P643An effective exercise intervention targeting breast cancer patients at greatest risk of cardiac dysfunction

Abstract

Introduction: Anthracycline chemotherapy (AC) is the mainstay of treatment for early-stage breast cancer. However, treatment is associated with changes in cardiac function and reductions in functional capacity (VO2peak). The late development of cardiotoxicity is common among survivors, and associated with poor prognosis. The assessment of cardiac functional reserve, may be a more sensitive marker of early cardiac injury and therefore better predictor of future events. Importantly, this marker of cardiovascular function is modifiable by a relatively inexpensive, yet effective intervention exercise training. Purpose: We sought to determine whether exercise measures identify those most at risk of developing cardiac dysfunction after AC and the effectiveness of exercise training in preventing cardiac dysfunction. Methods: 28 early-stage breast cancer patients undergoing AC were recruited into a non-randomised trial and allocated to exercise training (ET; 47±9 yrs, n=14) or usual care (UC; 53±9 years, n=14). Prior to and following completion of AC, testing included a maximal cardiopulmonary (VO2peak) test, resting echocardiography (left ventricular ejection fraction [LVEF] and global longitudinal strain [GLS]), cardiac biomarkers (BNP and troponin) and exercise cardiac magnetic resonance (CMR) imaging to determine the maximal cardiac output with exercise (cardiac reserve). The ET group completed 2 x 60 minute sessions/ week supervised aerobic and resistance exercise training program. Results: There was a 15% reduction in VO2peak in the UC group (22.0±5.9 to 18.8±5.9ml/kg/min), that was significantly attenuated by ET (27.4±5.7 to 26.3±5.3ml/kg/min, Group×Pre/Post P=0.024). We observed a modest reduction in resting (LVEF; 63±5 to 60±5%, Pre/Post P=0.002) and exercise cardiac function (cardiac reserve; ∼3%, Pre/Post P=0.06) following AC, which was not prevented by ET (interaction P>0.05). Troponin was increased following AC (2.9±1.3 to 28.5±22.4 ng/mL Pre/Post P<0.0001), while there were no significant changes in GLS (-20.0±2.0 to -19.6±2.0%) or BNP levels (37.9±34.6 to 38.4±21.5ng/L), and ET did not modify the response (P>0.05 for interaction). In a model containing age, LVEF and GLS, baseline cardiac reserve was the strongest predictor of poor functional capacity (VO2peak <18ml/kg/min) at completion of chemotherapy. Conclusion: Exercise CMR measures of cardiac reserve provided the best means of identifying patients at risk of AC-induced reductions in functional capacity. These reductions in functional capacity could be attenuated with regular exercise training during AC treatment for breast cancer.