Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:73

Article

Galan-Arriola, Carlos^1,2  Lobo, Manuel^1,3  Paul Vilchez-Tschischke, Jean^1,3  Lopez, Gonzalo J.¹  de Molina-Iracheta, Antonio¹  Perez-Martinez, Claudia⁴  Aguero, Jaume^1,2,5  Fernandez-Jimenez, Rodrigo^1,2,6  Martin-Garcia, Ana^2,7  Oliver, Eduardo¹  Villena-Gutierrez, Rocio¹  Pizarro, Gonzalo^1,2,3  Sanchez, Pedro L.^2,7  Fuster, Valentin^1,6  Sanchez-Gonzalez, Javier⁸  Ibanez, Borja^1,2,9 

[1] CNIC, Madrid, Spain

[2] Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain

[3] Complejo Hosp Ruber Juan Bravo, Madrid, Spain

[4] Fac Vet Leon, Leon, Spain

[5] Hosp Univ & Politecn La Fe, Dept Cardiol, Valencia, Spain

[6] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA

[7] Hosp Univ Salamanca, Dept Cardiol, IBSAL, Salamanca, Spain

[8] Philips Healthcare, Madrid, Spain

[9] IIS Fdn Jimenez Diaz Hosp, Cardiol Dept, Madrid, Spain

关键词: anthracycline;    cardio-oncology;    cardiotoxicity;    CMR;    doxorubicin;   

DOI  :  10.1016/j.jacc.2018.11.046

来源: Elsevier

【 摘 要 】

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 T-2 and T-1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS The earliest doxorubicin cardiotoxicity CMR parameter was T-2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T-1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T-2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T-1 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 T-2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T-2 prolongation occurs at a reversible disease stage. CONCLUSIONS T-2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T-1 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: 77991) (c) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/byncnd/4.0/).

【 授权许可】

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