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The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid\u2010range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on the European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Analysable data from 5608 participants were available in the Human Urinary Proteome database. The urinary peptide profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and controls matched for sex, age, estimated glomerular filtration rate, systolic and diastolic blood pressure, diabetes and hypertension were compared applying the Mann\u2013Whitney test, followed by correction for multiple testing. Unsupervised learning algorithms were applied to investigate groups of similar urinary profiles. A total of 577 urinary peptides significantly associated with HF were sequenced, 447 of which (77%) were collagen fragments.\n                      <jats:italic>In silico<\/jats:italic>\n                      analysis suggested that urinary biomarker abnormalities in HF principally reflect changes in collagen turnover and immune response, both associated with fibrosis. Unsupervised clustering separated study participants into two clusters, with 83% of non\u2010HF controls allocated to cluster 1, while 65% of patients with HF were allocated to cluster 2 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001). No separation based on HF subtype was detectable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Heart failure, irrespective of ejection fraction subtype, was associated with differences in abundance of urinary peptides reflecting collagen turnover and inflammation. These peptides should be studied as tools in early detection, prognostication, and prediction of therapeutic response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2195","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T21:46:14Z","timestamp":1619041574000},"page":"1875-1887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Urinary peptides in heart failure: a link to molecular pathophysiology"],"prefix":"10.1093","volume":"23","author":[{"given":"Tianlin","family":"He","sequence":"first","affiliation":[{"name":"Mosaiques Diagnostics GmbH  Hannover Germany"},{"name":"Institute for Molecular Cardiovascular Research (IMCAR) RWTH Aachen University Hospital  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Mischak","sequence":"additional","affiliation":[{"name":"Mosaiques Diagnostics GmbH  Hannover 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Cl\u00ednica Universidad de Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Department of Cardiology Athens University Hospital Attikon  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Mebazaa","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Unit\u00e9 Inserm MASCOT, Department of Anaesthesiology and Intensive Care, Saint Louis\u2010Lariboisi\u00e8re\u00a0\u2013\u00a0Fernand Widal University Hospital, Assistance Publique H\u00f4pitaux de Paris  Paris France"},{"name":"F\u2010CRIN INI\u2010CRCT (Cardiovascular and Renal Clinical Trialists)  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  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