Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study

Aim Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many...

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Autores: Revuelta-Lopez, E, Nunez, J, Gastelurrutia, P, Cediel, G, Januzzi, JL, Ibrahim, NE, Emdin, M, VanKimmenade, R, Pascual-Figal, D, Nunez, E, Gommans, F, Lupon, J, Bayes-Genis, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p4209
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/4209
Access Level:acceso abierto
Palabra clave:Heart failure
Neprilysin
Sacubitril
valsartan
Endorphins
alpha-Endorphin
gamma-Endorphin
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spelling Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot studyRevuelta-Lopez, ENunez, JGastelurrutia, PCediel, GJanuzzi, JLIbrahim, NEEmdin, MVanKimmenade, RPascual-Figal, DNunez, EGommans, FLupon, JBayes-Genis, AHeart failureNeprilysinSacubitrilvalsartanEndorphinsalpha-Endorphingamma-EndorphinAim Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short-term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment. Methods and results A total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of alpha- (alpha-EP), gamma-Endorphin (gamma-EP), and soluble NEP (sNEP) were measured using enzyme-linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating alpha-EP, gamma-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in alpha-EP nor gamma-EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Delta alpha-EP, Delta gamma-EP, and Delta sNEP between 30 days and baseline were 9.3 (-34 - 44), -3.0 (-46.0 - 18.9), and 0 units (-16.4 - 157.0), respectively. In a pre-post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Delta alpha-EP and Delta sNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Delta alpha-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. Conclusions These preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement.WILEY PERIODICALS, INC2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/4209ESC Heart FailureISSN: 20555822reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p42092026-06-07T16:35:31Z
dc.title.none.fl_str_mv Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
title Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
spellingShingle Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
Revuelta-Lopez, E
Heart failure
Neprilysin
Sacubitril
valsartan
Endorphins
alpha-Endorphin
gamma-Endorphin
title_short Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
title_full Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
title_fullStr Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
title_full_unstemmed Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
title_sort Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
dc.creator.none.fl_str_mv Revuelta-Lopez, E
Nunez, J
Gastelurrutia, P
Cediel, G
Januzzi, JL
Ibrahim, NE
Emdin, M
VanKimmenade, R
Pascual-Figal, D
Nunez, E
Gommans, F
Lupon, J
Bayes-Genis, A
author Revuelta-Lopez, E
author_facet Revuelta-Lopez, E
Nunez, J
Gastelurrutia, P
Cediel, G
Januzzi, JL
Ibrahim, NE
Emdin, M
VanKimmenade, R
Pascual-Figal, D
Nunez, E
Gommans, F
Lupon, J
Bayes-Genis, A
author_role author
author2 Nunez, J
Gastelurrutia, P
Cediel, G
Januzzi, JL
Ibrahim, NE
Emdin, M
VanKimmenade, R
Pascual-Figal, D
Nunez, E
Gommans, F
Lupon, J
Bayes-Genis, A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Heart failure
Neprilysin
Sacubitril
valsartan
Endorphins
alpha-Endorphin
gamma-Endorphin
topic Heart failure
Neprilysin
Sacubitril
valsartan
Endorphins
alpha-Endorphin
gamma-Endorphin
description Aim Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short-term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment. Methods and results A total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of alpha- (alpha-EP), gamma-Endorphin (gamma-EP), and soluble NEP (sNEP) were measured using enzyme-linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating alpha-EP, gamma-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in alpha-EP nor gamma-EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Delta alpha-EP, Delta gamma-EP, and Delta sNEP between 30 days and baseline were 9.3 (-34 - 44), -3.0 (-46.0 - 18.9), and 0 units (-16.4 - 157.0), respectively. In a pre-post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Delta alpha-EP and Delta sNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Delta alpha-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. Conclusions These preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/4209
url https://incliva.portalinvestigacion.com/publicaciones/4209
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY PERIODICALS, INC
publisher.none.fl_str_mv WILEY PERIODICALS, INC
dc.source.none.fl_str_mv ESC Heart Failure
ISSN: 20555822
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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