Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT

Abstract Background Preclinical studies have reported that a single treadmill session performed 24 h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24 h prior to treatment changes this response. Methods Breast cancer patients were randomized to either 30 min of vigorous-intensity exercise 24 h prior to the first doxorubicin treatment (n = 13), or no vigorous exercise for 72 h prior to treatment (control, n = 11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24–48 h after the treatment. Results Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p ≤ 0.01). Whereas systemic vascular resistance (p < 0.01) decreased, and ejection fraction (p = 0.02) and systolic strain rate (p < 0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p < 0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. Conclusion The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24 h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin. Background Preclinical studies have reported that a single treadmill session performed 24 h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24 h prior to treatment changes this response. Methods Breast cancer patients were randomized to either 30 min of vigorous-intensity exercise 24 h prior to the first doxorubicin treatment (n = 13), or no vigorous exercise for 72 h prior to treatment (control, n = 11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24–48 h after the treatment. Results Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p ≤ 0.01). Whereas systemic vascular resistance (p < 0.01) decreased, and ejection fraction (p = 0.02) and systolic strain rate (p < 0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p < 0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. Conclusion The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24 h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.