{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:27:27Z","timestamp":1753878447124,"version":"3.41.2"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Transplantation"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>We evaluated the effect of relative changes in combined tacrolimus and sirolimus (drug) levels, following sirolimus initiation, on outcomes in ambulatory heart transplantation (HTx) recipients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective analysis of HTx recipients who received tacrolimus, followed by sirolimus initiation, any time after HTx. We calculated the relative change in combined drug levels 1\u2010month post\u2010sirolimus initiation, relative to tacrolimus levels pre\u2010initiation, and categorized patients into decreased (\u226515% decrease), stable (&lt;15% decrease to\u00a0&lt;15% increase), or increased (\u226515% increase) groups. We compared, across the three groups, changes in post\u2010initiation estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) using one\u2010way ANOVA and \u0160id\u00e1k's post\u2010hoc analysis, as well as the individual and composite outcomes of new donor specific antibodies (DSA), acute cellular rejection (ACR), and all\u2010cause mortality using Fisher's exact test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Amongst 99 HTx recipients included, the median age was 53 years, time to sirolimus initiation was 1.5 years post\u2010HTx, and pre\u2010sirolimus eGFR was 52\u00a0mL\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup>. Nine patients had decreased, 15 stable, and 75 increased, relative combined drug levels. Relative change in eGFR was significantly higher in patients with decreased levels compared to patients with increased levels at 6 months post\u2010initiation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05), but this was not sustained at 12 months. There were no differences in LVEF change or in individual and composite risks for developing DSA, ACR, and all\u2010cause mortality at 12 months across the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Post\u2010sirolimus initiation, a relative decrease in combined drug levels, compared to increased levels, was associated with temporarily improved renal function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ctr.15184","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T10:25:50Z","timestamp":1699352750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Drug levels after sirolimus initiation and short\u2010term outcomes in ambulatory heart transplantation recipients"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1235-9557","authenticated-orcid":false,"given":"Mihail","family":"Kancharla","sequence":"first","affiliation":[{"name":"Peter Munk Cardiac Centre Ajmera Transplant Program University Health Network  Toronto Ontario Canada"},{"name":"Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lakshmi","family":"Kugathasan","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre Ajmera Transplant Program University Health Network  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"McDonald","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre Ajmera Transplant Program University Health Network  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2744-2696","authenticated-orcid":false,"given":"Ana Carolina","family":"Alba","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre Ajmera Transplant Program University Health Network  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.737965"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.12.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971\u20104065.176146"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2005.08.015"},{"key":"e_1_2_8_6_1","unstructured":"Rapamune Clinical Pharmacology.Pfizer: Medical Information. 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Accessed September 27 2023.https:\/\/www.kidney.org\/content\/mdrd\u2010study\u2010equation"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13076"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.06.236"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2010.09.014"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002702"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.942665"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2023.02.1358"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.01.1400"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15584"}],"container-title":["Clinical Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ctr.15184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T08:34:39Z","timestamp":1741768479000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ctr.15184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,7]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/ctr.15184"],"URL":"https:\/\/doi.org\/10.1111\/ctr.15184","archive":["Portico"],"relation":{},"ISSN":["0902-0063","1399-0012"],"issn-type":[{"type":"print","value":"0902-0063"},{"type":"electronic","value":"1399-0012"}],"subject":[],"published":{"date-parts":[[2023,11,7]]},"assertion":[{"value":"2023-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15184"}}