Cardiac MRI–based Subclinical Cardiac Dysfunction during 2 Years after Breast Cancer Irradiation: The MEDIRAD EARLY-HEART Study

Purpose: To evaluate the relationship between cardiac radiation doses and subclinical changes in cardiac function using cardiac MRI during 2 years of follow-up in patients with breast cancer treated with radiation therapy without chemotherapy after lumpectomy.

Materials and Methods: This prospective multicenter study (NCT03297346) enrolled female individuals with breast cancer treated with radiation therapy between December 2017 and September 2019. Participants underwent cardiac MRI at baseline, 6 months, and 24 months. Cardiac radiation doses were assessed for the whole heart (WH) and right and left ventricles (LV). A persistent decrease in LV global longitudinal strain (GLS) from baseline to the other two measurement points over the 2-year follow-up was considered an adverse subclinical change in cardiac function. Statistical analysis included Wilcoxon tests for continuous variables and odds ratios for risk assessment.

Results: The study included 138 female participants (mean age, 58.4 years ± 8.0 [SD]). Mean WH and LV doses were 1.42 Gy (IQR, 1.03-2.01) and 1.46 Gy (IQR, 0.64-2.34). At the 2-year follow-up, all participants had reduced LV end-diastolic volume (EDV) (-4.0% ± 13.2; P < .001) and stroke volume (-3.4% ± 15.2; P < .001), preserved LV ejection fraction, and increased LV remodeling (LV mass/EDV ratio) (4.2% ± 18.1; P < .04) without associated symptoms. Twenty-three (16.6%) participants showed a persistent decrease in LV GLS and received higher mean WH and LV doses compared with participants without persistent decrease in LV GLS (WH: 2.09 Gy [IQR, 1.50-2.45] vs 1.36 Gy [IQR, 1.01-1.87], P < .001; LV: 2.40 Gy [IQR, 1.09-2.88] vs 1.34 Gy [IQR, 0.63-2.02], P = .002). The relative changes in LV EDV and LV mass/EDV were -12.7% ± 9.0 versus -2.2% ± 13.3 ( P < .001) and 14.2% ± 15.5 versus 2.2% ± 18.1 ( P = .002), respectively, in participants with and without a persistent decrease in LV GLS. A higher WH cardiac radiation dose was associated with a higher risk of a persistent decrease in LV GLS (odds ratio, 1.09 [95% CI: 1.02, 1.16]).

Conclusion: In participants with recent breast cancer radiation therapy, a modest but persistent reduction in LV GLS over a 2-year follow-up period was associated with the cardiac radiation dose.

Keywords: Radiotherapy, Magnetic Resonance Imaging, Cardiotoxicity, Strain

Clinical trial registration no. NCT03297346