Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy

PURPOSE: Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (VO2peak). We sought to determine whether changes in VO2peak and cardiac function persisted at 12-months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk. METHODS: Women with breast cancer scheduled for AC (n=28) who participated in a non-randomized trial of exercise training (ET; n=14) or usual care (UC; n=14) during AC completed a follow-up evaluation 12-months post-AC completion (16-months from baseline). At baseline, 4-months, and 16-months, participants underwent a resting echocardiogram (left ventricular ejection fraction, LVEF; global longitudinal strain, GLS), a blood sample (troponin; b-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate (HR) and cardiac output (Qc) at rest, and during intense exercise. RESULTS: Seventeen women (UC: n=8; ET: n=9) completed evaluation at baseline, 4-months and 16-months. At 4-months, AC was associated with 18% and 6% reductions in VO2peak in the UC and ET groups respectively, that persisted at 16-months (UC: -16%; ET: -7%), and was not attenuated by ET (interaction, P=0.10). Exercise Qc was lower at 16-months compared to baseline and 4-months (P<0.001), which was due to a blunted augmentation of SV during exercise (P=0.032; a 14% reduction in peak SV), with no changes in HR response. There was a small reduction in resting LVEF (baseline to 4-months) and GLS (between 4-months and 16-months), and an increase in troponin (baseline to 4-months), but only exercise Qc was associated with VO2peak (R=0.47, P<0.01). CONCLUSION: Marked reductions in VO2peak persisted 12-months following anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function. CLINICAL TRIAL REGISTRATION: ACTRN12616001602415.