Cargando…
Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial
AIMS: Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3′5′ monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload....
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801941/ https://www.ncbi.nlm.nih.gov/pubmed/31093657 http://dx.doi.org/10.1093/eurheartj/ehz240 |
_version_ | 1783460697448906752 |
---|---|
author | Morrow, David A Velazquez, Eric J DeVore, Adam D Prescott, Margaret F Duffy, Carol I Gurmu, Yared McCague, Kevin Rocha, Ricardo Braunwald, Eugene |
author_facet | Morrow, David A Velazquez, Eric J DeVore, Adam D Prescott, Margaret F Duffy, Carol I Gurmu, Yared McCague, Kevin Rocha, Ricardo Braunwald, Eugene |
author_sort | Morrow, David A |
collection | PubMed |
description | AIMS: Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3′5′ monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). METHODS AND RESULTS: PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome. CONCLUSION: Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1–4 weeks. CLINICAL TRIALS REGISTRATION: NCT 02554890 clinical.trials.gov |
format | Online Article Text |
id | pubmed-6801941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68019412019-10-24 Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial Morrow, David A Velazquez, Eric J DeVore, Adam D Prescott, Margaret F Duffy, Carol I Gurmu, Yared McCague, Kevin Rocha, Ricardo Braunwald, Eugene Eur Heart J Fast Track Clinical Research AIMS: Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3′5′ monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). METHODS AND RESULTS: PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome. CONCLUSION: Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1–4 weeks. CLINICAL TRIALS REGISTRATION: NCT 02554890 clinical.trials.gov Oxford University Press 2019-10-21 2019-05-15 /pmc/articles/PMC6801941/ /pubmed/31093657 http://dx.doi.org/10.1093/eurheartj/ehz240 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Fast Track Clinical Research Morrow, David A Velazquez, Eric J DeVore, Adam D Prescott, Margaret F Duffy, Carol I Gurmu, Yared McCague, Kevin Rocha, Ricardo Braunwald, Eugene Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial |
title | Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial |
title_full | Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial |
title_fullStr | Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial |
title_full_unstemmed | Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial |
title_short | Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial |
title_sort | cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the pioneer-hf trial |
topic | Fast Track Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801941/ https://www.ncbi.nlm.nih.gov/pubmed/31093657 http://dx.doi.org/10.1093/eurheartj/ehz240 |
work_keys_str_mv | AT morrowdavida cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT velazquezericj cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT devoreadamd cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT prescottmargaretf cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT duffycaroli cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT gurmuyared cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT mccaguekevin cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT rocharicardo cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial AT braunwaldeugene cardiovascularbiomarkersinpatientswithacutedecompensatedheartfailurerandomizedtosacubitrilvalsartanorenalaprilinthepioneerhftrial |