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.

In clinically stable HFrEF patients, MICT is an effective therapy to attenuate LV remodeling with the greatest benefits occurring with long-term (≥6 months) training. HIIT performed for 2 to 3 months is superior to control, but not MICT, for improvement of LVEF.

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Background. Peak oxygen consumption (VO 2 ) is reduced in women with a history of breast cancer (BC). We measured leg blood flow, oxygenation, bioenergetics, and muscle composition in women with BC treated with anthracycline chemotherapy (n = 16, mean age: 56 years) and age-and body mass index-matched controls (n = 16). Materials and Methods. Whole-body peak VO 2 was measured during cycle exercise. 31 Phosphorus magnetic resonance (MR) spectroscopy was used to measure muscle bioenergetics during and after incremental to maximal plantar flexion exercise (PFE). MR imaging was used to measure lower leg blood flow, venous oxygen saturation (S v O 2 ), and VO 2 during submaximal PFE, and abdominal, thigh, and lower leg intermuscular fat (IMF) and skeletal muscle (SM). Results. Whole-body peak VO 2 was significantly lower in BC survivors versus controls (23.1 AE 7.5 vs. 29.5 AE 7.7 mL/kg/minute).Muscle bioenergetics and mitochondrial oxidative capacity were not different between groups. No group differences were found during submaximal PFE for lower leg blood flow, S v O 2 , or VO 2 . The IMF-to-SM ratio was higher in the thigh and lower leg in BC survivors (0.36 AE 0.19 vs. 0.22 AE 0.07, p = .01; 0.10 AE 0.06 vs. 0.06 AE 0.02, p = .03, respectively) and were inversely related to whole-body peak VO 2 (r = −0.71, p = .002; r = −0.68, p = .003, respectively) . In the lower leg, IMF-to-SM ratio was inversely related to VO 2 and O 2 extraction during PFE. Conclusion. SM bioenergetics and oxidative capacity in response to PFE are not impaired following anthracycline treatment. Abnormal SM composition (increased thigh and lower leg IMF-to-SM ratio) may be an important contributor to reduced peak VO 2 during whole-body exercise among anthracycline-treated BC survivors. The Oncologist 2020;25:e852-e860 Implications for Practice: Peak oxygen consumption (peak VO 2 ) is reduced in breast cancer (BC) survivors and is prognostic of increased risk of cardiovascular disease-related and all-cause mortality. Results of this study demonstrated that in the presence of deficits in peak VO 2 1 year after anthracycline therapy, skeletal muscle bioenergetics and oxygenation are not impaired. Rather, body composition deterioration (e.g., increased ratio of intermuscular fat to skeletal muscle) may contribute to reduced exercise tolerance in anthracycline BC survivors. This finding points to the importance of lifestyle interventions including caloric restriction and exercise training to restore body composition and cardiovascular health in the BC survivorship setting.

We hypothesize that the reduced peak aerobic power (peak VO2) following heart transplantation (HT) is due to impaired cardiovascular and skeletal muscle function, and its improvement with short-term (≤1 year) exercise training is primarily due to favorable skeletal muscle adaptations. Further, the increased peak VO2 with long-term (>2 years) training is primarily mediated by cardiac (sympathetic) reinnervation.