{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T14:52:28Z","timestamp":1785595948635,"version":"3.56.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":506,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Young Scientists","award":["21K16091"],"award-info":[{"award-number":["21K16091"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We measured the serum HE4 levels of 55 participants (80.8 \u00b1 8.0 years old, male n = 26, 46%) with severe AS prior to surgical aortic valve replacement (n = 31, 56%) or transcatheter aortic valve implantation (n = 24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3 years. Serum HE4 levels were positively correlated with computed tomography\u2013extracellular volume (CT-ECV) values (r = 0.53, P = 0.004). Kaplan\u2013Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P = 0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81\u201331.1; P = 0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3 years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62\u20130.90; P = 0.003).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14845","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:43:37Z","timestamp":1716857017000},"page":"2924-2932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human Epididymis Protein 4 is a Useful Predictor of Post-Operative Prognosis in Patients with Severe Aortic Stenosis"],"prefix":"10.1093","volume":"11","author":[{"given":"Fumihiko","family":"Ogata","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-9373","authenticated-orcid":false,"given":"Shinsuke","family":"Hanatani","sequence":"additional","affiliation":[{"name":"Department of 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Graduate School of Medical Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisanori","family":"Kanazawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Hoshiyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Takashio","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University , Kumamoto 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