Abstract

Introduction: Detection of cancer therapy-related cardiac dysfunction (CTRCD) is a cornerstone of heart failure (HF) risk assessment. However, it is unclear how closely CTRCD definitions reflect typical HF features of reduced exercise tolerance (VO 2 peak) and blunted cardiac reserve. Hypothesis: Standard CTRCD metrics (resting LVEF and GLS) will show poor agreement with reduced VO 2 peak and changes in cardiac reserve following anthracycline chemotherapy (AC). Methods: This analysis used baseline (pre-AC) and 12-month assessments from a randomized trial of exercise training in breast cancer patients (n=104) undergoing AC ± anti-HER2 therapy. Assessments included resting echocardiography (LVEF and GLS), cardiopulmonary exercise testing (VO 2 peak) and exercise cardiac magnetic resonance (peak cardiac output [CO], stroke volume [SV] and LVEF [LVEF peak ]). CTRCD was defined as ≥10% absolute decline in LVEF to a value <50%, >15% decline in GLS, and a ≥10% decline in VO 2 peak from pre-AC. Results: Seventy-nine participants (76%) completed pre-AC and 12-month assessments, 14 of whom (18%) met LVEF and 30 (38%) met GLS CTRCD criteria (10% met both criteria). In addition to declines in resting LVEF and GLS, these participants showed a reduction in LVEF peak , but no change in peak SV, CO or VO 2 peak (Figure 1A-B). In contrast, 19 participants (24%) had a ≥10% VO 2 peak decline (-17% vs Pre-AC, P<0.001) that coincided with a decline in peak SV (-6%, P=0.03), and LVEF peak (-11%, P=0.02), with no significant change in resting LVEF or GLS (Figure 1C). Of those who met VO 2 peak criteria, only three (16%) and five (26%) met LVEF or GLS criteria, respectively, and only one met all three criteria. Conclusions: Whilst capturing reduced global LV systolic function, CTRCD definitions are insensitive to meaningful declines in VO 2 peak and cardiac reserve. Incorporating measures of VO 2 peak into CTRCD surveillance may improve HF risk stratification in breast cancer survivors.

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