P644Changes in cardiopulmonary fitness and cardiac reserve 12-months following anthracycline-based chemotherapy with or without concurrent exercise training

Abstract

Background: Anthracycline chemotherapy (AC) has been associated with reductions in cardiac function that increases long-term risk of heart failure. The assessment of the heart's response to exercise may represent a useful tool for detecting small reductions in cardiac function following AC. We have previously shown that AC is associated with a substantial reduction in cardiopulmonary fitness (VO2peak) that occurs alongside a subtle reduction in the heart's contractile response to exercise. However the degree to which these changes recover following the completion of AC is unknown. Purpose: To investigate the changes in cardiopulmonary fitness (VO2peak) and cardiac function at 12 months following AC compared to pre-AC values. Methods: 28 women with breast cancer who had self-selected to undergo 12- weeks of aerobic and resistance training twice per week during AC (ET; n=14) or usual care during AC (UC; n=14) were asked to return for an evaluation of fitness and cardiac function 12 months from AC completion. Outcomes include VO2peak measured from a maximal cardiopulmonary exercise test (CPET); and stroke volume (SV), heart rate (HR) and cardiac output (CO) measured at rest, and during high-intensity supine cycling, using exercise cardiac magnetic resonance imaging (exCMR). These measures were compared to changes in resting left-ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) assessed by echocardiography. Results: To date, 13/28 women (UC: n=5; ET: n=8) have completed follow-up evaluation. AC was associated with persistent reductions in fitness at 12-months in both the UC than ET (16% vs. 8% reduction from baseline values, P<0.01), and these declines were not attenuated by ET (interaction, P=0.42) - see Figure. These declines in fitness were associated with 13% reductions in exCMR peak CO as compared with pre-AC values (14.0±2.5L/min vs 12.2±2.6 L/min, P<0.01). The reduction in CO appears to be due to a 14% reduction in the SV response to exercise (98.3±12.1 ml vs 84.6±14.5 ml, P<0.01), whereas heart rate was not different between pre-AC and 12 months (146±16 bpm vs 151±17bpm, P=0.70). No differences were found between resting CO and SV from pre-AC to 12-months (P=0.25 and P=0.27 respectively), however there was a reduction in LVEF and GLS from 64.3±4.8% to 59.2±6.8% (P<0.05) and -19.8±1.6 to - 18.4±1.4 (P<0.01) respectively. (Figure Presented) Conclusion: Substantial reductions in cardiopulmonary fitness persisted 9 months following AC-based chemotherapy, and these could not be attenuated by 12-weeks of exercise training during AC. Reductions in fitness were associated with reductions in peak cardiac output during exercise. These measures may identify patients at greatest risk of heart failure during survivorship and highlight the potential need for ongoing surveillance of cardiac and functional capacity.