Fluoropyrimidine Cardiotoxicity: Role of Uridine Triacetate and Pharmacogenomic Insights from a Case of 5-FU-Induced Cardiogenic Shock.

Authors

Simone Filomia, Marco Giuseppe Del Buono, Gianluigi Saponara, Cristina Aurigemma, Riccardo Marano, Eleonora Moliterno, Giampaolo Tortora, Angelo Minucci, Lisa Salvatore, Paolo Maurizio Soave, Francesco Burzotta, Tommaso Sanna

Published in

Journal of cardiovascular pharmacology. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

Fluoropyrimidines, including 5-fluorouracil and capecitabine, are widely used antimetabolite agents and remain central to the treatment of several solid tumors, particularly gastrointestinal malignancies. However, they are a well-established cause of chemotherapy-related cardiotoxicity. Although coronary vasospasm is the best recognized manifestation, fluoropyrimidine cardiotoxicity encompasses a broad clinical spectrum, ranging from chest pain and arrhythmias to acute heart failure, and, rarely, fulminant cardiogenic shock. This review discusses severe fluoropyrimidine-associated cardiotoxicity through the illustrative presentation of a young woman without prior cardiovascular disease who developed acute biventricular dysfunction and cardiogenic shock shortly after first exposure to FOLFIRINOX, requiring temporary mechanical circulatory support. Administration of uridine triacetate within the recommended therapeutic window was associated with rapid recovery of ventricular function. Cardiac magnetic resonance imaging demonstrated diffuse myocardial edema without late gadolinium enhancement, consistent with reversible toxic-inflammatory myocardial injury. Expanded genomic analysis identified DPYD and TYMS variants not detected by standard pretreatment pharmacogenetic screening. We herein examine the pathophysiological mechanisms of fluoropyrimidine cardiotoxicity, the rationale for uridine triacetate in severe presentations, and the potential role of expanded pharmacogenomic profiling within a precision cardio-oncology framework.

PMID:
42407011
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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