{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T09:54:59Z","timestamp":1783590899298,"version":"3.55.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":878,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hutter Family Professorship"},{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril\/valsartan (Sac\/Val) treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Mid-regional pro-adrenomedullin (MR-proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac\/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac\/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12\u2009months in the HFrEF cohort. Median (Q1\u2013Q3) baseline MR-proADM concentrations were 0.80 (0.59\u20130.99) nmol\/L in HFrEF and 0.88 (0.68\u20131.20) nmol\/L in HFpEF. After 12\u2009weeks of treatment with Sac\/Val, MR-proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan-treated patients (median 2%). Greater increases in MR-proADM were associated with higher Sac\/Val doses. Changes in MR-proADM correlated weakly with changes in N-terminal pro-B-type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR-proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MR-proAD concentrations rise substantially following treatment with Sac\/Val, in contrast to no change from valsartan. Change in MR-proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of heart failure.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: PROVE-HF ClinicalTrials.gov Identifier: NCT02887183, PARAMOUNT ClinicalTrials.gov Identifier: NCT00887588.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2957","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T04:47:31Z","timestamp":1688446051000},"page":"1396-1405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Changes in Mid-Regional Pro-Adrenomedullin During Treatment with Sacubitril\/Valsartan"],"prefix":"10.1093","volume":"25","author":[{"given":"Peder L.","family":"Myhre","sequence":"first","affiliation":[{"name":"Division of Medicine, Akershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of Oslo , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Cardiology Division, Massachusetts General Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Kulac","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret F.","family":"Prescott","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceutical Corporation , East Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Michael","family":"Felker","sequence":"additional","affiliation":[{"name":"Duke University Medical School and Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical School , Jackson, MS ,","place":["USA"]},{"name":"Baylor Scott and White Research Institute , Dallas, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana L.","family":"Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University , Philadelphia, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute and University of Montreal , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center , Charleston, SC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Ward","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceutical Corporation , East Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Januzzi","sequence":"additional","affiliation":[{"name":"Cardiology Division, Massachusetts General Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]},{"name":"Baim Institute for 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