{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:45:53Z","timestamp":1790790353121,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,2,19]]},"abstract":"\n Background<\/jats:title>\n \n Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure (\n CHF<\/jats:styled-content>\n ) patients. However, temporal patterns during the course of\n CHF<\/jats:styled-content>\n , and especially the trajectory before an adverse event, are unknown. We studied the prognostic value of temporal patterns of 14 cardiac remodeling biomarker candidates in stable patients with CHF from the Bio\u2010SHiFT (Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis) study.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n In 263\n CHF<\/jats:styled-content>\n patients, we performed trimonthly blood sampling during a median follow\u2010up of 2.2\u00a0years. For the analysis, we selected all baseline samples, the 2 samples closest to the primary end point (\n PE<\/jats:styled-content>\n ), or the last sample available for end point\u2013free patients. Thus, in 567 samples, we measured suppression of tumorigenicity\u20102, galectin\u20103, galectin\u20104, growth differentiation factor\u201015, matrix metalloproteinase\u20102, 3, and 9, tissue inhibitor metalloproteinase\u20104, perlecan, aminopeptidase\u2010N, caspase\u20103, cathepsin\u2010D, cathepsin\u2010Z, and cystatin\u2010B. The\n PE<\/jats:styled-content>\n was a composite of cardiovascular mortality, heart transplantation, left ventricular assist device implantation, and\n HF<\/jats:styled-content>\n hospitalization. Associations between repeatedly measured biomarker candidates and the\n PE<\/jats:styled-content>\n were investigated by joint modeling. Median age was 68 (interquartile range: 59\u201376) years with 72% men; 70 patients reached the\n PE<\/jats:styled-content>\n . Repeatedly measured suppression of tumorigenicity\u20102, galectin\u20103, galectin\u20104, growth differentiation factor\u201015, matrix metalloproteinase\u20102 and 9, tissue inhibitor metalloproteinase\u20104, perlecan, cathepsin\u2010D, and cystatin\u2010B levels were significantly associated with the\n PE<\/jats:styled-content>\n , and increased as the\n PE<\/jats:styled-content>\n approached. The slopes of biomarker trajectories were also predictors of clinical outcome, independent of their absolute level. Associations persisted after adjustment for clinical characteristics and pharmacological treatment. Suppression of tumorigenicity\u20102 was the strongest predictor (hazard ratio: 7.55 per\n SD<\/jats:styled-content>\n difference, 95%\n CI<\/jats:styled-content>\n : 5.53\u201310.30), followed by growth differentiation factor\u201015 (4.06, 2.98\u20135.54) and matrix metalloproteinase\u20102 (3.59, 2.55\u20135.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Temporal patterns of remodeling biomarker candidates predict adverse clinical outcomes in\n CHF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier:\n NCT<\/jats:styled-content>\n 01851538.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009555","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T10:08:30Z","timestamp":1550138910000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Temporal Patterns of 14 Blood Biomarker candidates of Cardiac Remodeling in Relation to Prognosis of Patients With Chronic Heart Failure\u2014The Bio\u2010SHiFT Study"],"prefix":"10.1161","volume":"8","author":[{"given":"Elke","family":"Bouwens","sequence":"first","affiliation":[{"name":"Department of Cardiology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milos","family":"Brankovic","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Mouthaan","sequence":"additional","affiliation":[{"name":"Olink Proteomics Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Baart","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Rizopoulos","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"van Boven","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadir","family":"Caliskan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Manintveld","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasmus MC Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjeerd","family":"Germans","sequence":"additional","affiliation":[{"name":"Department of Cardiology Northwest Clinics Alkmaar the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Ramshorst","sequence":"additional","affiliation":[{"name":"Department of Cardiology Northwest Clinics Alkmaar the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Umans","sequence":"additional","affiliation":[{"name":"Department of Cardiology Northwest Clinics Alkmaar the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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