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.

Automated summary

This study found that anthracycline-treated breast cancer survivors exhibited abnormalities in peak exercise cardiac function and thigh muscle fatty infiltration, which were associated with VO(2)peak. Myocardial fibrosis and thigh muscle fatty infiltration negatively influence VO(2)peak, indicating impaired cardiac reserve and oxygen extraction post-anthracyclines.