Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays

Nasrien E. Ibrahim, Cian P. McCarthy, Shreya Shrestha, Hanna K. Gaggin, Renata Mukai, Jackie Szymonifka, Fred S. Apple, John C Jr. Burnett, Seethalakshmi Iyer, James L. Januzzi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP 1-108 , or C-type natriuretic peptide (CNP) is not well understood. Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP 1-108 , and CNP were measured over 3 visits. Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP 1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.

Original languageEnglish (US)
Pages (from-to)1273-1284
Number of pages12
JournalJournal of the American College of Cardiology
Volume73
Issue number11
DOIs
StatePublished - Mar 26 2019

Fingerprint

Neprilysin
Natriuretic Peptides
Atrial Natriuretic Factor
Brain Natriuretic Peptide
C-Type Natriuretic Peptide
LCZ 696
Therapeutics
Heart Failure

Keywords

  • biomarkers
  • heart failure
  • natriuretic peptides
  • neprilysin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Ibrahim, N. E., McCarthy, C. P., Shrestha, S., Gaggin, H. K., Mukai, R., Szymonifka, J., ... Januzzi, J. L. (2019). Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays. Journal of the American College of Cardiology, 73(11), 1273-1284. https://doi.org/10.1016/j.jacc.2018.12.063

Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays. / Ibrahim, Nasrien E.; McCarthy, Cian P.; Shrestha, Shreya; Gaggin, Hanna K.; Mukai, Renata; Szymonifka, Jackie; Apple, Fred S.; Burnett, John C Jr.; Iyer, Seethalakshmi; Januzzi, James L.

In: Journal of the American College of Cardiology, Vol. 73, No. 11, 26.03.2019, p. 1273-1284.

Research output: Contribution to journalArticle

Ibrahim, NE, McCarthy, CP, Shrestha, S, Gaggin, HK, Mukai, R, Szymonifka, J, Apple, FS, Burnett, JCJ, Iyer, S & Januzzi, JL 2019, 'Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays', Journal of the American College of Cardiology, vol. 73, no. 11, pp. 1273-1284. https://doi.org/10.1016/j.jacc.2018.12.063
Ibrahim NE, McCarthy CP, Shrestha S, Gaggin HK, Mukai R, Szymonifka J et al. Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays. Journal of the American College of Cardiology. 2019 Mar 26;73(11):1273-1284. https://doi.org/10.1016/j.jacc.2018.12.063
Ibrahim, Nasrien E. ; McCarthy, Cian P. ; Shrestha, Shreya ; Gaggin, Hanna K. ; Mukai, Renata ; Szymonifka, Jackie ; Apple, Fred S. ; Burnett, John C Jr. ; Iyer, Seethalakshmi ; Januzzi, James L. / Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays. In: Journal of the American College of Cardiology. 2019 ; Vol. 73, No. 11. pp. 1273-1284.
@article{cdf38e7bd94e4cfeb0f90ebd43c632b5,
title = "Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays",
abstract = "Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP 1-108 , or C-type natriuretic peptide (CNP) is not well understood. Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP 1-108 , and CNP were measured over 3 visits. Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8{\%}). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188{\%}) compared with those with lower baseline concentrations (+44{\%}); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP 1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.",
keywords = "biomarkers, heart failure, natriuretic peptides, neprilysin",
author = "Ibrahim, {Nasrien E.} and McCarthy, {Cian P.} and Shreya Shrestha and Gaggin, {Hanna K.} and Renata Mukai and Jackie Szymonifka and Apple, {Fred S.} and Burnett, {John C Jr.} and Seethalakshmi Iyer and Januzzi, {James L.}",
year = "2019",
month = "3",
day = "26",
doi = "10.1016/j.jacc.2018.12.063",
language = "English (US)",
volume = "73",
pages = "1273--1284",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "11",

}

TY - JOUR

T1 - Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays

AU - Ibrahim, Nasrien E.

AU - McCarthy, Cian P.

AU - Shrestha, Shreya

AU - Gaggin, Hanna K.

AU - Mukai, Renata

AU - Szymonifka, Jackie

AU - Apple, Fred S.

AU - Burnett, John C Jr.

AU - Iyer, Seethalakshmi

AU - Januzzi, James L.

PY - 2019/3/26

Y1 - 2019/3/26

N2 - Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP 1-108 , or C-type natriuretic peptide (CNP) is not well understood. Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP 1-108 , and CNP were measured over 3 visits. Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP 1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.

AB - Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP 1-108 , or C-type natriuretic peptide (CNP) is not well understood. Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP 1-108 , and CNP were measured over 3 visits. Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP 1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.

KW - biomarkers

KW - heart failure

KW - natriuretic peptides

KW - neprilysin

UR - http://www.scopus.com/inward/record.url?scp=85062731100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062731100&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2018.12.063

DO - 10.1016/j.jacc.2018.12.063

M3 - Article

VL - 73

SP - 1273

EP - 1284

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 11

ER -