Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure
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 pep...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:226259 |
| Acceso en línea: | https://ddd.uab.cat/record/226259 https://dx.doi.org/urn:doi:10.1002/ehf2.12607 |
| Access Level: | acceso abierto |
| Palabra clave: | Heart failure Neprilysin Sacubitril/valsartan Endorphins α-Endorphin γ-Endorphin |
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oai:ddd.uab.cat:226259 |
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España |
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| 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 |
| spellingShingle |
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure Revuelta-López, Elena|||0000-0001-8962-5936 Heart failure Neprilysin Sacubitril/valsartan Endorphins α-Endorphin γ-Endorphin |
| title_short |
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure |
| title_full |
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure |
| title_fullStr |
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure |
| title_full_unstemmed |
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure |
| title_sort |
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure |
| dc.creator.none.fl_str_mv |
Revuelta-López, Elena|||0000-0001-8962-5936 Núñez, Julio|||0000-0003-1672-7119 Gastelurrutia, Paloma|||0000-0001-6974-9210 Januzzi, James L. Ibrahim, Nasrien E. Emdin, Michele VanKimmenade, Roland Pascual-Figal, DA.|||0000-0002-4993-9540 Núñez, Eduardo Gommans, Frank Lupón, Josep|||0000-0002-5601-9611 Bayés-Genís, Antoni|||0000-0002-3044-197X |
| author |
Revuelta-López, Elena|||0000-0001-8962-5936 |
| author_facet |
Revuelta-López, Elena|||0000-0001-8962-5936 Núñez, Julio|||0000-0003-1672-7119 Gastelurrutia, Paloma|||0000-0001-6974-9210 Januzzi, James L. Ibrahim, Nasrien E. Emdin, Michele VanKimmenade, Roland Pascual-Figal, DA.|||0000-0002-4993-9540 Núñez, Eduardo Gommans, Frank Lupón, Josep|||0000-0002-5601-9611 Bayés-Genís, Antoni|||0000-0002-3044-197X |
| author_role |
author |
| author2 |
Núñez, Julio|||0000-0003-1672-7119 Gastelurrutia, Paloma|||0000-0001-6974-9210 Januzzi, James L. Ibrahim, Nasrien E. Emdin, Michele VanKimmenade, Roland Pascual-Figal, DA.|||0000-0002-4993-9540 Núñez, Eduardo Gommans, Frank Lupón, Josep|||0000-0002-5601-9611 Bayés-Genís, Antoni|||0000-0002-3044-197X |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Heart failure Neprilysin Sacubitril/valsartan Endorphins α-Endorphin γ-Endorphin |
| topic |
Heart failure Neprilysin Sacubitril/valsartan Endorphins α-Endorphin γ-Endorphin |
| description |
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. 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 α- (α-EP), γ-Endorphin (γ-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 α-EP, γ-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in α-EP nor γ-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 Δα-EP, Δγ-EP, and ΔsNEP 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. Δα-EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. 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 |
2 2020-01-01 2020 2020-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/226259 https://dx.doi.org/urn:doi:10.1002/ehf2.12607 |
| url |
https://ddd.uab.cat/record/226259 https://dx.doi.org/urn:doi:10.1002/ehf2.12607 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-483 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-84324-C2-1-R Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01487 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18-00256 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIC18-00014 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD16-00111-0006 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CB16-11-00403 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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1869405692218048512 |
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Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failurea pilot studyRevuelta-López, Elena|||0000-0001-8962-5936Núñez, Julio|||0000-0003-1672-7119Gastelurrutia, Paloma|||0000-0001-6974-9210Januzzi, James L.Ibrahim, Nasrien E.Emdin, MicheleVanKimmenade, RolandPascual-Figal, DA.|||0000-0002-4993-9540Núñez, EduardoGommans, FrankLupón, Josep|||0000-0002-5601-9611Bayés-Genís, Antoni|||0000-0002-3044-197XHeart failureNeprilysinSacubitril/valsartanEndorphinsα-Endorphinγ-EndorphinSacubitril/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. 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 α- (α-EP), γ-Endorphin (γ-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 α-EP, γ-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in α-EP nor γ-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 Δα-EP, Δγ-EP, and ΔsNEP 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. Δα-EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. 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. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/226259https://dx.doi.org/urn:doi:10.1002/ehf2.12607reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-483Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-84324-C2-1-RInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01487Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18-00256Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIC18-00014Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD16-00111-0006Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CB16-11-00403open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2262592026-06-06T12:50:31Z |
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