Association between global longitudinal strain and cardiopulmonary fitness in patients with breast cancer

Abstract Background Anthracycline and trastuzumab therapies improve survival in the cancer population, but are limited by treatment induced cardiotoxicity. Echocardiography derived global longitudinal strain (GLS) permits more sensitive detection of cardiotoxicity than left ventricular ejection fraction (LVEF). However, the clinical implication of a reduction in GLS in cancer survivors is unknown. Purpose To define the association between GLS and cardiopulmonary fitness in women with breast cancer immediately post cancer therapy. Methods Women with HER2+ early stage breast cancer (EBC, Stage I-III) receiving anthracyclines followed by trastuzumab were recruited prospectively and followed between January 2015 and December 2019 with echocardiography during therapy. Left ventricular peak systolic GLS (GE EchoPAC, 3 apical views) and 3D-LVEF were measured prior to anthracyclines, and after completion of trastuzumab at 12 months. Exercise capacity was measured using a supine bicycle cardiopulmonary exercise test. Results of exercise testing at end of treatment were compared between patients with and without reduced GLS (absolute value ≤18% vs >18%) at the end of therapy. Results Amongst 128 women, 43 (34%) had a GLS ≤18% at the end of trastuzumab therapy. Baseline patient demographics including tumor characteristics and cardiac risk factors were similar between those with normal and abnormal GLS. During treatment 33 (25.8%) participants developed cardiotoxicity defined by the CREC criteria based on 3D-LVEF. Significant baseline (pre-cancer treatment) differences were found between groups for GLS (GLS 21.2±1.8 vs 19.6±2.2, p18% and GLS ≤18% respectively at the completion of trastuzumab. Compared to those with GLS >18% those with GLS ≤18% had lower VO2peak (17.4±3.8 mL.kg-1.min-1 versus 20.2±4.9 mL.kg-1.min-1, p=0.001) despite similar effort (respiratory exchange ratio 1.14 versus 1.12, p=0.30). GLS following therapy (β coefficient: −0.596, SE 0.255; p=0.02) and age (β coefficient: −0.115, SE 0.057; p=0.047) were the only parameters associated with VO2peak after adjusting for relevant confounding factors. Conclusion A significant proportion of women receiving cancer therapy for HER2+ EBC had reduced GLS at end of treatment. Abnormal GLS at the end of cancer treatment was associated with lower VO2peak. Reduced VO2peak is strongly associated with late-occurring cardiovascular events and should