Early Detection of Anthracycline-Induced Cardiotoxicity in Breast Cancer Survivors With T2 Cardiac Magnetic Resonance.

May 2019 1 Maryam B. Lustberg, MD, MPH* Raquel Reinbolt, MD* Daniel Addison, MD* Amy S. Ruppert, PhD Sean Moore, MD Sarah Carothers, MS Anupama Suresh, BS Hiranmoy Das, PhD Michael Berger, PharmD Bhuvaneswari Ramaswamy, MD Robert Wesolowski, MD Philip Binkley, MD, MPH Subha V. Raman, MD Charles L. Shapiro, MD Anthracycline therapy remains a mainstay for breast cancer (BC) and many other cancers. However, anthracyclines incur a >5-fold risk of incident heart failure. Substrate for heart failure is myocardial fibrosis that is preceded by myocardial edema/inflammation, as supported by preclinical studies of anthracycline-induced myocardial damage.1 Loss of endothelial progenitor cells (EPCs) has also been viewed as a contributor to myocardial damage.2 However, detection of early changes via blood biomarkers for better risk stratification in humans remains challenging.3 Recently, cardiac magnetic resonance (CMR) has been successfully applied in the detection of post-treatment anthracycline-induced fibrosis through T1 mapping, paralleling decline in left ventricular ejection fraction (LVEF). 4 Given preclinical evidence that myocardial edema precedes fibrosis in anthracyclineinduced myocardial damage,1 we tested the hypothesis that myocardial edema could be detected using the CMR relaxation parameter T2, comparing its value to EPC assay in human subjects receiving anthracyline therapy for BC. We prospectively enrolled at Ohio State University’s James Comprehensive Cancer Center consecutive women with nonmetastatic BC initiating doxorubicincontaining regimens who provided written informed consent to participate in this Institutional Review Board-approved longitudinal study. Females ≥18 years old treated with doxorubicin for neoadjuvant or adjuvant therapy were included. We excluded those with prior anthracycline exposure, coronary disease, or contraindication to magnetic resonance. Scans were performed pretreatment (≥2 weeks before anthracycline initiation), post-cycle 1 of treatment (early), and 2 to 4 weeks after the last cycle of anthracyclines (post-treatment). Correlative biomarkers, including high-sensitivity TnI (troponin-I), BNP (brain natriuretic peptide), and peripheral blood EPCs were assayed from blood collected at the time of imaging. EPCs were processed according to previously published protocols.5 Available CMR data from those presenting for follow-up CMR>1-year post-anthracycline initiation were also assessed. The primary outcome was changed in myocardial T2 following anthracycline initiation. All scans were completed at 1.5 Tesla (Magnetom Avanto, Siemens Healthcare). Acquired data included conventional cine imaging in longand short-axis planes, T2 mapping, and late gadolinium enhancement imaging following intravenous administration of 0.2 mmol/kg gadolinium-based contrast agent (gadopentetate dimeglumine). CMR analyses were performed blinded to clinical information and included: (1) computation of ventricular volumes from endocardial contour delineation, (2) circumferential systolic strain computation using feature tracking (VVI, Siemens), (3) identification of maximum T2 by manual segmentation, and (4) recording of presence or absence of myocardial damage by full width at half-maximum segmentation of late gadolinium enhancement images. Pretreatment characteristics are described with mean±SD for continuous variables and © 2019 American Heart Association, Inc. RESEARCH LETTER