Background Anthracycline chemotherapy may be associated with decreased cardiac function and functional capacity measured as the peak oxygen uptake during exercise ([Formula: see text] peak). We sought to determine (a) whether a structured exercise training program would attenuate reductions in [Formula: see text] peak and (b) whether exercise cardiac imaging is a more sensitive marker of cardiac injury than the current standard of care resting left ventricular ejection fraction (LVEF). Methods Twenty-eight patients with early stage breast cancer undergoing anthracycline chemotherapy were able to choose between exercise training (mean ± SD age 47 ± 9 years, n = 14) or usual care (mean ± SD age 53 ± 9 years, n = 14). Measurements performed before and after anthracycline chemotherapy included cardiopulmonary exercise testing to determine [Formula: see text] peak and functional disability ([Formula: see text] peak < 18 ml/min/kg), resting echocardiography (LVEF and global longitudinal strain), cardiac biomarkers (troponin and B-type natriuretic peptide) and exercise cardiac magnetic resonance imaging to determine stroke volume and peak cardiac output. The exercise training group completed 2 × 60 minute supervised exercise sessions per week. Results Decreases in [Formula: see text] peak during chemotherapy were attenuated with exercise training (15 vs. 4% reduction, P = 0.010) and fewer participants in the exercise training group met the functional disability criteria after anthracycline chemotherapy compared with those in the usual care group (7 vs. 50%, P = 0.01). Compared with the baseline, the peak exercise heart rate was higher and the stroke volume was lower after chemotherapy ( P = 0.003 and P = 0.06, respectively). There was a reduction in resting LVEF (from 63 ± 5 to 60 ± 5%, P = 0.002) and an increase in troponin (from 2.9 ± 1.3 to 28.5 ± 22.4 ng/mL, P < 0.0001), but no difference was observed between the usual care and exercise training group. The baseline peak cardiac output was the strongest predictor of functional capacity after anthracycline chemotherapy in a model containing age and resting cardiac function (LVEF and global longitudinal strain). Conclusions The peak exercise cardiac output can identify patients at risk of chemotherapy-induced functional disability, whereas current clinical standards are unhelpful. Functional disability can be prevented with exercise training.

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Purpose Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak 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 nonrandomized 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; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, 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 V˙O2peak in the UC and ET groups, respectively, which 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 with 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 heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R 2 = 0.47, P < 0.01). Conclusion Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function. Clinical Trial Registration: ACTRN12616001602415.