Subclinical left ventricular dysfunction post radiotherapy in breast cancer: Speckle-tracking echocardiography detects dose-related longitudinal strain changes after irradiation (BACCARAT study)

Background Breast cancer radiotherapy (BC RT) can be associated with long-term, silent and lately detected cardiotoxicity. Longitudinal strain (LS), based on 2D speckle-tracking echocardiography (2DSTE) can early detect subclinical left ventricular dysfunction. Little is known on the association between RT-induced cardiac doses and LS changes. Purpose To analyze the relationship between cardiac doses and LS changes after BC RT. Methods BACCARAT is a monocentric prospective cohort study that included BC patients treated with RT without chemotherapy. Global LS, in particular in the mid-layer of the myocardium (GLS-mid), was measured with 2DSTE before RT and 6 months after RT. We evaluated radiation doses to whole heart, left ventricle (LV), left anterior descending coronary artery (LAD). A subclinical event of cardiotoxicity “decreased GLS-mid ≥ 10%” was defined as a relative decrease ≥ 10%. Results We included 94 patients (18 right-sided BC, 76 left-sided BC) aged 59 ± 8 years. Mean doses to the heart, LV and LAD were respectively: 3.0 ± 1.3 Gy, 6.6 ± 3.2 Gy and 16.5 ± 7.5 Gy for the left-sided BC; 0.6 ± 0.5 Gy, 0.2 ± 0.2 Gy and 0.3 ± 0.5 Gy for the right-sided BC. Left-sided BC had a significant decrease in GLS-mid (%relative change = 9.0%, P = 0.02); the event “decreased GLS-mid ≥ 10%” was detected in 50% of left-sided BC and 38% in the right-sided group. We observed dose-response relationships with mean doses to the heart, the LV and the LAD in univariate analysis, that remained marginally significant in adjusted analysis for mean LV dose and indicating an increase of the event by 11% for each increase of 1 Gy in LV dose (OR = 1.11, 95%CI [0.98–1.26]). Conclusion This is the first study to establish dose-response relationships between BC RT-induced cardiac doses and decreased LS 6 months after RT. With longer follow-up, it remains to be determined whether these dose-related changes are confirmed and if detection of this subclinical LV dysfunction is related to clinical outcome.