{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:24:31Z","timestamp":1782977071506,"version":"3.54.5"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU\/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart","award":["116074"],"award-info":[{"award-number":["116074"]}]},{"DOI":"10.13039\/501100018722","name":"Jaap Schouten Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018722","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Noordwest Academie"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to provide insights into underlying mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 2.5\u20132.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular [left ventricular ejection fraction (LVEF), global longitudinal strain (GLS)] and left atrial function [left atrial reservoir strain (LASr)] and elevated LAP (E\/e\u02b9 ratio &amp;gt;15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E\/e\u02b9 ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: cystatin-D, fibulin-5, and HSP40.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Circulating proteins show varying associations with different echocardiographic parameters in patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjci\/jeae098","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T14:27:51Z","timestamp":1712672871000},"page":"1206-1215","source":"Crossref","is-referenced-by-count":9,"title":["The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure"],"prefix":"10.1093","volume":"25","author":[{"given":"S","family":"Abou Kamar","sequence":"first","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"},{"name":"The Netherlands Heart Institute , Moreelsepark 1, 3511 EP Utrecht , The Netherlands"},{"name":"Department of Cardiology, Franciscus Gasthuis & Vlietland , Kleiweg 500, 3045 PM Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Andrzejczyk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T B","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"},{"name":"Department of Biostatistics, University Medical Center Rotterdam, Erasmus University , Dr. Molewaterplein 40, 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"},{"name":"Department of Cardiology, Franciscus Gasthuis & Vlietland , Kleiweg 500, 3045 PM Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y S","family":"Aga","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"},{"name":"Department of Cardiology, Franciscus Gasthuis & Vlietland , Kleiweg 500, 3045 PM Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"de Bakker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K M","family":"Akkerhuis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Geleijnse","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"Brugts","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3713-4136","authenticated-orcid":false,"given":"O","family":"Sorop","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0900","authenticated-orcid":false,"given":"D","family":"Rizopoulos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The Netherlands"},{"name":"Department of Biostatistics, University Medical Center Rotterdam, Erasmus University , Dr. Molewaterplein 40, 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F W","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Medical Center, Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2559-7128","authenticated-orcid":false,"given":"E","family":"Boersma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Thorax Center, Cardiovascular Institute, University Medical Center Rotterdam , Room Na-316, PO Box 2040 3000 CA Rotterdam , The 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