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Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure : a pilot study
Revuelta-López, Elena (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Núñez, Julio (Hospital Clínic Universitari (València))
Gastelurrutia, Paloma (Institut Germans Trias i Pujol)
Januzzi, James L. (Massachusetts General Hospital and Cardiometabolic Trials, Baim Institute for Clinical Research)
Ibrahim, Nasrien E. (Massachusetts General Hospital and Cardiometabolic Trials, Baim Institute for Clinical Research)
Emdin, Michele (Scuola Superiore Sant'Anna, Fondazione Toscana Gabriele Monasterio)
VanKimmenade, Roland (Radboud University Medical Centre)
Pascual-Figal, Domingo (Universidad de Murcia)
Núñez, Eduardo (Hospital Clínic Universitari (València))
Gommans, Frank (Radboud University Medical Centre)
Lupón, Josep (Universitat Autònoma de Barcelona. Departament de Medicina)
Bayés-Genís, Antoni (Universitat Autònoma de Barcelona. Departament de Medicina)

Fecha: 2020
Resumen: 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.
Ayudas: Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR483
Ministerio de Economía y Competitividad SAF2017-84324-C2-1-R
Instituto de Salud Carlos III PI17-01487
Instituto de Salud Carlos III PI18-00256
Instituto de Salud Carlos III PIC18-00014
Instituto de Salud Carlos III RD16-00111-0006
Instituto de Salud Carlos III CB16-11-00403
Nota: Altres ajuts: This work was supported in part by Fundació La Marató de TV3 (201516-10, 201502-30), Societat Catalana de Cardiologia, "la Caixa" Banking Foundation.
Nota: Altres ajuts: PERIS/SLT002-16-00234
Derechos: Aquest 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. Creative Commons
Lengua: Anglès
Documento: Article ; recerca ; Versió publicada
Materia: Heart failure ; Neprilysin ; Sacubitril/valsartan ; Endorphins ; α-Endorphin ; γ-Endorphin
Publicado en: ESC Heart Failure, Vol. 7 (february 2020) , p. 559-566, ISSN 2055-5822

DOI: 10.1002/ehf2.12607
PMID: 32045114


8 p, 940.6 KB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Artículos > Artículos de investigación
Artículos > Artículos publicados

 Registro creado el 2020-07-06, última modificación el 2023-03-06



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