{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:13:18Z","timestamp":1788415998574,"version":"build-2803163510"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anthracyclines are highly effective chemotherapeutic agents but are limited by cumulative, dose-dependent cardiotoxicity, leading to strict lifetime exposure thresholds. L-Annamycin is a next-generation liposomal anthracycline designed to preserve antitumor efficacy while reducing cardiotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a pooled analysis of cardiac safety data from five sponsor- and investigator-initiated clinical trials evaluating L-Annamycin in acute myelogenous leukemia (AML) and metastatic soft tissue sarcoma (STS). Cardiac monitoring included serial electrocardiograms, cardiac biomarkers (troponin I\/T), and transthoracic echocardiography with left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) assessment. All cardiac data were independently evaluated by a cardio-oncology laboratory at the Cleveland Clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ninety patients were included, with paired echocardiographic data available in 78. Median cumulative L-Annamycin dose was 660\u2005mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (IQR 450\u20131,080). Baseline and post-treatment LVEF did not differ significantly (60.6% vs. 60%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.84). No associations were observed between change in LVEF and cumulative dose or age. Serial ECG, troponin, and GLS assessments showed no treatment-related cardiotoxicity. These findings were observed despite cumulative exposures exceeding conventional anthracycline lifetime limits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this pooled analysis of patients with AML and STS, L-Annamycin was not associated with clinical or subclinical evidence of cardiotoxicity at cumulative doses exceeding traditional anthracycline thresholds. These data support continued clinical evaluation of L-Annamycin as a potentially safer anthracycline platform.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1817847","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:21:46Z","timestamp":1788412906000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac safety of L-Annamycin: a pooled analysis of five clinical trials"],"prefix":"10.3389","volume":"13","author":[{"given":"Ziad","family":"Zalaquett","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Waymack","sequence":"additional","affiliation":[{"name":"Department of Statistics, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1002\/cmdc.202000131","article-title":"Antitumour anthracyclines: progress and perspectives","volume":"15","author":"Martins-Teixeira","year":"2020","journal-title":"ChemMedChem"},{"key":"B2","year":""},{"key":"B3","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1042\/CS20200301","article-title":"Molecular mechanisms of anthracycline cardiovascular toxicity","volume":"135","author":"Narezkina","year":"2021","journal-title":"Clin Sci (Lond)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.jacc.2014.06.1167","article-title":"Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities","volume":"64","author":"Vejpongsa","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.ejca.2023.02.019","article-title":"Anthracycline-induced cardiotoxicity - 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