{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:40:00Z","timestamp":1785559200421,"version":"3.56.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":670,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:00:00Z","timestamp":1707004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Pathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We report data from a representative subcohort of the prospective Singapore Heart Failure Outcomes and Phenotypes (SHOP), including patients with HFrEF (EF\u2009&amp;lt;40%, n\u2009=\u2009217), HFpEF (EF\u2009\u226550%, n\u2009=\u2009213), and age- and sex-matched controls without HF (n\u2009=\u2009216). We measured 92 biomarkers using a proximity extension assay and assessed cardiac structure and function in all participants using echocardiography. We used multi-block projection to latent structure analysis to integrate clinical, echocardiographic, and biomarker variables. Candidate biomarker targets were cross-referenced with small-molecule and drug databases. The total cohort had a median age of 65\u2009years (interquartile range 60\u201371), and 50% were women. Protein profiles strongly discriminated patients with HFrEF (area under the curve [AUC]\u2009=\u20090.89) and HFpEF (AUC\u2009=\u20090.94) from controls. Phenomics analyses identified unique druggable inflammatory markers in HFpEF from the tumour necrosis factor receptor superfamily (TNFRSF), which were positively associated with hypertension, diabetes, and increased posterior and relative wall thickness. In HFrEF, interleukin (IL)-8 and IL-6 were possible targets related to lower EF and worsening renal function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified pathophysiological mechanisms related to increased cardiac wall thickness parameters and potentially druggable inflammatory markers from the TNFRSF in HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3156","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T03:04:01Z","timestamp":1707275041000},"page":"841-850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Distinguishing Heart Failure with Reduced Ejection Fraction from Heart Failure with Preserved Ejection Fraction: A Phenomics Approach"],"prefix":"10.1093","volume":"26","author":[{"given":"Bart J.","family":"van Essen","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganash N.","family":"Tharshana","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health and The National University Health System , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Ouwerkerk","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute , Amsterdam ,","place":["The Netherlands"]},{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poh Suan Daniel","family":"Yeo","sequence":"additional","affiliation":[{"name":"Tan Tock Seng Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sim","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazlur","family":"Jaufeerally","sequence":"additional","affiliation":[{"name":"Duke-NUS Medical School , Singapore ,","place":["Singapore"]},{"name":"Department of Medicine, Singapore General Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hean Yee","family":"Ong","sequence":"additional","affiliation":[{"name":"Khoo Teck Puat Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieng Hsi","family":"Ling","sequence":"additional","affiliation":[{"name":"National University Heart Centre Singapore, Cardiovascular Research Institute Singapore, National University of Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinna Kar Nee","family":"Soon","sequence":"additional","affiliation":[{"name":"Khoo Teck Puat Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao Guang Sheldon","family":"Lee","sequence":"additional","affiliation":[{"name":"National University Heart Centre Singapore, Cardiovascular Research Institute Singapore, National University of Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Leong","sequence":"additional","affiliation":[{"name":"Changi General Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seet Yoong","family":"Loh","sequence":"additional","affiliation":[{"name":"Tan Tock Seng Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"San Tan","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrishan J.","family":"Ramachandra","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore ,","place":["Singapore"]},{"name":"Changi General Hospital , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Hausenloy","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore ,","place":["Singapore"]},{"name":"Changi General Hospital , Singapore ,","place":["Singapore"]},{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oi Wai","family":"Liew","sequence":"additional","affiliation":[{"name":"National University Heart Centre Singapore, Cardiovascular Research Institute Singapore, National University of Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Chong","sequence":"additional","affiliation":[{"name":"National University Heart Centre Singapore, Cardiovascular Research Institute Singapore, National University of Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S.P.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]},{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore , Singapore ,","place":["Singapore"]},{"name":"Duke-NUS Medical School , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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