{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:42:58Z","timestamp":1790664178506,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011102","name":"European Commission FP7 Programme","doi-asserted-by":"publisher","award":["EU-MASCARA project grant HEALTH-2011-278249"],"award-info":[{"award-number":["EU-MASCARA project grant HEALTH-2011-278249"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"European Commission FP7 Programme","doi-asserted-by":"publisher","award":["HOMAGE project grant HEALTH-2012-305507"],"award-info":[{"award-number":["HOMAGE project grant HEALTH-2012-305507"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["EU\u2010MASCARA project grant HEALTH\u20102011\u2010278249"],"award-info":[{"award-number":["EU\u2010MASCARA project grant HEALTH\u20102011\u2010278249"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["HOMAGE project grant HEALTH\u20102012\u2010305507"],"award-info":[{"award-number":["HOMAGE project grant HEALTH\u20102012\u2010305507"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial fibrosis is characterized by excessive cross-linking and deposition of collagen type I and is involved in left ventricular stiffening and left ventricular diastolic dysfunction (LVDD). We investigated whether the effect of spironolactone on LVDD in patients with heart failure with preserved ejection fraction (HFpEF) depends on its effects on collagen cross-linking and\/or deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We investigated 381 HFpEF patients from the multicentre, randomized, placebo-controlled Aldo-DHF trial with measures of the E:e' ratio. The ratio of serum carboxy-terminal telopeptide of collagen type I to serum matrix metalloproteinase-1 (CITP:MMP-1, an inverse index of myocardial collagen cross-linking) and serum carboxy-terminal propeptide of procollagen type I (PICP, a direct index of myocardial collagen deposition) were determined at baseline and after 1-year treatment with spironolactone 25\u2009mg once daily or placebo. Patients were classified by CITP:MMP-1 and PICP tertiles at baseline. While CITP:MMP-1 tertiles at baseline interacted (P\u2009&amp;lt;\u20090.05) with spironolactone effect on E:e', PICP tertiles did not. In fact, while spironolactone treatment did not modify E:e' in patients with lower CITP:MMP-1 levels, this ratio was significantly reduced in the remaining spironolactone-treated patients. In addition, PICP was unchanged in patients with lower CITP:MMP-1 levels but was reduced in the remaining spironolactone-treated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A biochemical phenotype of high collagen cross-linking identifies HFpEF patients resistant to the beneficial effects of spironolactone on LVDD. It is suggested that excessive collagen cross-linking, which stabilizes collagen type I fibres, diminishes the ability of spironolactone to reduce collagen deposition in these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1194","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T16:43:21Z","timestamp":1525106601000},"page":"1290-1299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Biomarker-Based Phenotyping of Myocardial Fibrosis Identifies Patients with Heart Failure with Preserved Ejection Fraction Resistant to the Beneficial Effects of Spironolactone: Results From the Aldo-DHF Trial"],"prefix":"10.1093","volume":"20","author":[{"given":"Susana","family":"Ravassa","sequence":"first","affiliation":[{"name":"University of Navarra, CIMA, Program of Cardiovascular Diseases, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, CIBERCV, Carlos III Institute of Health , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Trippel","sequence":"additional","affiliation":[{"name":"Institute for Internal Medicine and Cardiology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Bach","sequence":"additional","affiliation":[{"name":"Institute for Internal Medicine and Cardiology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bachran","sequence":"additional","affiliation":[{"name":"Institute for Internal Medicine and Cardiology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"University of Navarra, CIMA, Program of Cardiovascular Diseases, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, CIBERCV, Carlos III Institute of Health , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"University of Navarra, CIMA, Program of Cardiovascular Diseases, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, CIBERCV, Carlos III Institute of Health , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Wachter","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University of G\u00f6ttingen Medical Centre G\u00f6ttingen, G\u00f6ttingen, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Hasenfuss","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University of G\u00f6ttingen Medical Centre G\u00f6ttingen, G\u00f6ttingen, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Delles","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna F.","family":"Dominiczak","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical 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