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

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO(2)peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy similar to 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T-1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO(2)peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 +/- 9 vs 57 +/- 10 mL/m(2), 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 T-1 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 VO(2)peak. Peak SV (R-2 = 65%) and thigh muscle fat fraction (R-2 = 68%) were similarly strong independent predictors of VO(2)peak 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 VO(2)peak.