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The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib\u2010CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post\u2010baseline plasma samples of 60\u2009MM patients treated with carfilzomib\u2010based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post\u2010baseline\/baseline metabolite ratios that differ between the CVAE and no\u2010CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T\u2010UDCA) in CVAE patients at baseline (odds ratio [OR]\u2009=\u20090.47, 95% confidence interval [CI]\u2009=\u20090.21\u20130.94, <jats:italic>p<\/jats:italic>\u2009=\u20090.044) compared with the no\u2010CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver\u2010operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR\u2009=\u20090.56, 95% CI\u2009=\u20090.31\u20130.87, <jats:italic>p<\/jats:italic>\u2009=\u20090.023) was significantly lower in post\u2010baseline\/baseline ratios of CVAE patients compared with no\u2010CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib\u2010CVAE and potential cardioprotective strategies.<\/jats:p>","DOI":"10.1111\/cts.13828","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T04:45:57Z","timestamp":1716525957000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolomic signatures of carfilzomib\u2010related cardiotoxicity in patients with multiple myeloma"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-2322","authenticated-orcid":false,"given":"Samia","family":"Shabnaz","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1877-8697","authenticated-orcid":false,"given":"Trang N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6735-6990","authenticated-orcid":false,"given":"Roy","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-4441","authenticated-orcid":false,"given":"Samuel M.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-009X","authenticated-orcid":false,"given":"Timothy J.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-1093","authenticated-orcid":false,"given":"Marwa","family":"Tantawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Fradley","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-7245","authenticated-orcid":false,"given":"Mohammed E.","family":"Alomar","sequence":"additional","affiliation":[{"name":"Department of Malignant Hematology H. 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