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Universidades","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective \u03b23 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The \u03b23 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50\u2009mg daily, titrated till 200\u2009mg daily, n = 39) or placebo (n = 41) for 16\u2009weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] \u22120.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SPHERE-HF is the first clinical trial to assess the potential benefit of \u03b23 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2745","type":"journal-article","created":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T23:28:18Z","timestamp":1668986898000},"page":"373-385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["\u03b23 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Associated with Heart Failure (SPHERE-HF): A Double Blind, Placebo-Controlled, Randomized Clinical Trial"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1718-2424","authenticated-orcid":false,"given":"Ana","family":"Garc\u00eda-\u00c1lvarez","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona ,","place":["Spain"]},{"name":"Universitat de Barcelona , Barcelona ,","place":["Spain"]},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Blanco","sequence":"additional","affiliation":[{"name":"Universitat de Barcelona , Barcelona ,","place":["Spain"]},{"name":"Department of Pulmonary Medicine, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Garc\u00eda-Lunar","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Cardiology Department, University Hospital La Moraleja , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Jord\u00e0","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Rodriguez-Arias","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Fern\u00e1ndez-Friera","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]},{"name":"Centro de 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,","place":["Spain"]},{"name":"Department of Cardiology, University Hospital Puerta de Hierro-IDIPHISA, Universidad Aut\u00f3noma de Madrid (UAM) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Torrecilla","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pereda","sequence":"additional","affiliation":[{"name":"Universitat de Barcelona , Barcelona ,","place":["Spain"]},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Department of Cardiovascular Surgery, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona 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de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Department of Cardiology, University Hospital Puerta de Hierro-IDIPHISA, Universidad Aut\u00f3noma de Madrid (UAM) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan F","family":"Delgado","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Department of Cardiology, University Hospital 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria i+12, Universdad Complutense , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Mirabet","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Cardiology 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Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan A.","family":"Barber\u00e1","sequence":"additional","affiliation":[{"name":"Universitat de Barcelona , Barcelona ,","place":["Spain"]},{"name":"Department of Pulmonary Medicine, Hospital Cl\u00ednic Barcelona-IDIBAPS , Barcelona ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"IIS-Fundaci\u00f3n Jim\u00e9nez Diaz University Hospital , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the SPHERE-HF Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"2026010913120503700_ejhf2745-bib-0001","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0735-1097(00)01102-5","article-title":"Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure","volume":"37","author":"Ghio","year":"2001","journal-title":"J Am Coll Cardiol"},{"key":"2026010913120503700_ejhf2745-bib-0002","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jacc.2011.06.076","article-title":"Pulmonary pressures and death in heart failure: a community study","volume":"59","author":"Bursi","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"2026010913120503700_ejhf2745-bib-0003","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1164\/rccm.201503-0529OC","article-title":"Pulmonary hypertension in heart failure. 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