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

Amy A Kirkham,Richard B Thompson,Edith Pituskin,Justin G Grenier,Rhys I Beaudry,John R Mackey,D Ian Paterson,Mark J Haykowsky

doi:10.1038/s41598-021-93241-5

Amy A Kirkham, Richard B Thompson + Show 6 more

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https://doi.org/10.1038/s41598-021-93241-5

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Journal: Scientific Reports	Publication Date: Jul 7, 2021
Citations: 13	License type: open-access

Affiliation: University of Toronto, University of Alberta

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.

Highlights

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)
Reduced V O2peak may be due to a lower peak exercise cardiac output (CO, product of stroke volume, SV, and heart rate, HR) and/or a lower arteriovenous oxygen difference (avO2diff), which indicates lower oxygen extraction by the exercising muscles
Two prior studies, using indirect estimates or submaximal measures of SV during exercise, suggest that anthracycline chemotherapy has a detrimental effect on exercise SV in BCS2,5

Summary

Introduction

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). Magnetic resonance imaging (MRI) is the gold standard for quantification of resting and exercise cardiac function and enables acquisition of complementary central and peripheral metrics with implications for V O2peak, including global longitudinal strain (GLS), and tissue characterization of the myocardium and the exercising thigh muscles (such as T1 mapping metric of fibrosis and fatty infiltration, respectively). We performed a comprehensive MRI study with an overarching goal of characterizing peak exercise cardiac function, including GLS, myocardial T 1 time, and thigh muscle fatty infiltration (measured by fat fraction) and their relationships with V O2peak among anthracycline-treated BCS. The final objective was to determine whether exercise cardiac function and avO2diff mediate the relationship between cardiac and skeletal muscle tissue characteristics and V O2peak

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