Early Detection of Anthracycline-Induced Cardiotoxicity

RESEARCH HIGHLIGHT

Early Detection of Anthracycline-Induced Cardiotoxicity in Breast Cancer Survivors

August 2019

Anthracycline therapy is a mainstay for breast cancer and many other cancers, but it is associated with a rate of incident heart failure more than five times the average. Preclinical studies of anthracycline-induced myocardial damage show that the substrate for heart failure is myocardial fibrosis preceded by myocardial edema or inflammation. Loss of endothelial progenitor cells (EPCs) may also contribute to myocardial damage. The detection of early changes via blood biomarkers is challenging. However, recently, cardiac magnetic resonance (CMR) has been successfully used to detect post-treatment anthracycline-induced fibrosis through T1 mapping, paralleling a decline in left ventricular ejection fraction (LVEF).

Maryam Lustberg and her colleagues at The Ohio State University’s James Comprehensive Cancer Center conducted a prospective study1 to test the hypothesis that myocardial edema could be detected by the CMR relaxation parameter T2, comparing its value to EPC assay in women receiving anthracyline therapy for breast cancer. They studied 29 women, aged 54±10 years, with nonmetastatic breast cancer who were receiving neoadjuvant or adjuvant therapy with the anthracycline doxorubicin and who had not had previous anthracycline exposure, coronary disease, or a contraindication for magnetic resonance. The median cumulative doxorubicin dose was 237.1±7.6 mg/m2. Scans were performed two weeks or more prior to treatment, after the first cycle of treatment, and 2 to 4 weeks after the last treatment cycle. 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. Available CMR data from those presenting for follow-up CMR more than a year after beginning therapy were also assessed. The primary outcome was a change in myocardial T2 following anthracycline initiation.

After the first anthracycline treatment, there was no significant change in LVEF or circumferential strain. However, there was a significant increase in myocardial T2 by 3.3±0.8 ms. After completion of doxorubicin treatment (post fourth cycle), there remained no difference in LVEF or circumferential strain, but myocardial T2 had further increased by 5.4±0.8 ms. There were no significant changes in TnI or BNP across visits. Compared to similar healthy volunteers, these breast cancer patients had lower baseline EPC levels, but no significant difference in EPC levels before and after doxorubicin initiation. There was also no clear correlative pattern between EPC morphology and CMR or cardiac biomarker parameters. Among those with late CMRs, LVEF decreased, with 35% (6) seeing more than a 10% decline. Three women (18%) developed late gadolinium enhancement, but there was no significant correlation between early change in T2, circumferential strain, and late LVEF decline.

Women undergoing anthracycline therapy are at high risk for significant reductions in LVEF. The presence of early myocardial inflammation as shown by T2 increase appears to be associated with anthracycline administration, even before fibrosis, abnormal strain, and decline in LVEF. The study is limited by its focus on breast cancer patients only, the sample size, and lack of long-term follow-up. But it does suggest that patients undergoing anthracycline therapy are at high risk for significant reductions in LVEF. Subsequent research should evaluate the prognostic role of CMR-derived early myocardial T2 change as a potential biomarker — as a basis for risk stratification and a target for cardioprotective strategies.
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1The methodology and results were published as a research letter in Circulation: Cardiovascular Imaging, 2019 May; 12(5):e008777. The data that support the findings are available from the corresponding author upon reasonable request: Subha V. Raman, MD, Division of Cardiovascular Medicine, Ohio State University, 473 W 12th Ave, Suite 200, Columbus, OH 43210.