{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:59:33Z","timestamp":1789419573599,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigates the link between circulating proteins and rate\u2010corrected QT (QTc) interval in patients with heart failure with reduced ejection fraction (HFrEF) and their association with cardiovascular outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>We analyzed 197 HFrEF patients from the prospective Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis (Bio\u2010SHiFT) study, all in sinus rhythm at baseline. Baseline QTc intervals were calculated and corrected for broad QRS complexes (&gt;120\u00a0ms) using Bogossian's formula. Using the Somalogic\u2010SomaScan Assay, 1105 cardiovascular\u2010related proteins were measured in baseline blood samples. Linear regression identified 11 biomarkers significantly associated with QTc interval (false discovery rate [FDR]\u00a0&lt;\u00a00.05), adjusted for age, sex, and QT\u2010prolonging medications. These included interleukin\u20101 receptor\u2010like 1 (ST2) and angiopoietin\u20102. An additional four biomarkers showed potential relevance (FDR\u00a0&lt;\u00a00.1). Cox regression analysis revealed that five biomarkers\u2014ST2, angiopoietin\u20102, atrial natriuretic factor, insulin\u2010like growth factor\u2010binding protein 7 (IGFBP7), and carbonic anhydrase 4 (CA4)\u2014were significantly associated with the composite clinical endpoint of cardiovascular death, heart transplantation, left ventricular assist device implantation, and heart failure hospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Several cardiovascular proteins are associated with the QTc interval and adverse cardiovascular events in HFrEF patients. The observed associations highlight pathways such as inflammation, fibrosis, and angiogenesis, which may contribute to QTc prolongation and adverse outcomes in HFrEF. Further research is warranted to reveal underlying mechanisms and clinical applicability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This study is the first to investigate the association between QTc interval and a broad panel of over 1000 plasma proteins in patients with heart failure with reduced ejection fraction (HFrEF).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We identified 11 proteins significantly linked to QTc interval, five of which also demonstrated prognostic relevance for adverse cardiovascular outcomes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The associated biomarkers are linked to inflammation, fibrosis, and angiogenesis\u2010related pathways. These findings provide novel insights into the multifactorial mechanisms associated with QTc prolongation, potentially due to direct or indirect effects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The results emphasize the potential of circulating biomarkers as tools for understanding the pathophysiological processes associated with QTc prolongation and arrhythmogenesis in heart failure.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Moreover, the identification of interleukin\u20101 receptor\u2010like 1 (ST2), angiopoietin\u20102, atrial natriuretic factor, IGFBP7, and carbonic anhydrase 4 (CA4) as shared markers of QTc interval prolongation and adverse outcomes underscores their clinical utility as both diagnostic and prognostic biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/prca.70020","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T07:41:02Z","timestamp":1756885262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic Biomarkers Are Linked to QTc Interval in Patients With Chronic Heart Failure"],"prefix":"10.1002","volume":"20","author":[{"given":"Myl\u00e8ne","family":"Barry\u2010Loncq de Jong","sequence":"first","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun B.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"},{"name":"Department of Biostatistics, Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Abou Kamar","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navin","family":"Suthahar","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"van Boven","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Martijn","family":"Akkerhuis","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"van der Spek","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics, Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Katsikis","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor A. 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M.","family":"Umans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Northwest Clinics  Alkmaar the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boersma","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers, Department of Cardiology University of Amsterdam  Amsterdam the Netherlands"},{"name":"Health Data Research UK and Institute of Health Informatics University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper J.","family":"Brugts","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sing\u2010Chien","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-9745","authenticated-orcid":false,"given":"Isabella","family":"Kardys","sequence":"additional","affiliation":[{"name":"Department of Cardiology Thorax Center Cardiovascular Institute Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/1947-2714.179931"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-023-02173-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2022.11.016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.11.041"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-019-1134-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.13796"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2017.10.008"},{"issue":"14","key":"e_1_2_9_9_1","first-page":"1787","article-title":"ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. 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