2026-05-21T23:47:53Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/89912024-10-31T11:39:56Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Galan-Arriola, Carlos author Lobo-Gonzalez, Manuel author Vilchez, Jean Paul author Lopez-Martin, Gonzalo J. author Molina-Iracheta, Antonio author Pérez-Martínez, Claudia author Aguero, Jaume author Fernandez-Jimenez, Rodrigo author Martín-García, Ana author Oliver, Eduardo author Villena-Gutierrez, Rocio author Pizarro, Gonzalo author Sánchez, Pedro L author Fuster, Valentin author Sanchez-Gonzalez, Javier author Ibáñez, Borja author 2019-02 BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy. J Am Coll Cardiol. 2019; 73(7):779-791 10.1016/j.jacc.2018.11.046 1558-3597 0735-1097 Journal of the American College of Cardiology 30784671 http://hdl.handle.net/20.500.12105/8991 CMR Anthracycline Cardio-oncology Cardiotoxicity Doxorubicin Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity