Cardiac and skeletal muscle predictors of impaired cardiorespiratory fitness post-anthracycline chemotherapy for breast cancer

Abstract

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (− 30.4 ± 2.2 vs − 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.

Longitudinal Changes in Skeletal Muscle Metabolism, Oxygen Uptake, and Myosteatosis During Cardiotoxic Treatment for Early-Stage Breast Cancer

“… 6 Further, thigh myosteatosis had similar predictive power for low pulmonary VO 2 peak as exercise cardiac function. 7 We also found that greater myosteatosis in the lower leg was associated with decreased O 2 consumption and extraction by the lower leg during submaximal plantarflexion (ie, toe-pointing) exercise. 6 Similarly, while the functional implications are not yet clear, we found that intermuscular fat within the paraspinal (postural) muscles significantly increased within the first 3 months of trastuzumab-containing chemotherapy and persisted to 12 months.…”

Can We Estimate Cardiorespiratory Fitness in Breast Cancer Survivors Without Exercise?

“…By leveraging primarily cardiac features to predict peak V o 2 , the investigators have focused on the “cardiocentric” contributors to fitness, thereby providing a clear mechanistic link between subclinical cardiac dysfunction and impaired fitness in this population. In contrast, as CRF is determined by multisystem organ health ( 9 ), a focus on cardiac abnormalities may result in a large amount of unexplained variation in peak V o 2 , as observed in this study. Incorporating data from simple exercise studies that can be performed in the physician’s office (eg, exercise treadmill or 6-minute walk tests) may yield models with better predictive performance in future studies.…”

Physical Inactivity, Adverse Body Composition, and Cardiac Function in Breast Cancer Survivors

“…Moreover, among anthracycline-treated early-stage breast cancer survivors, we found that impaired cardiac reserve and thigh muscle fatty infiltration were associated with impaired oxygen extraction, both contributing to reduced V o 2peak . 12 In a secondary analysis of the MANTICORE (Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research) study, we observed a significant increase in fatty infiltration of skeletal muscle and increased visceral fat without concurrent change in BMI. 13 BMI categories of overweight and obese are considered CVD risk factors, but BMI cannot distinguish body fat percentage or fat location.…”