A A Kirkham1, R E Shave2, K A Bland3, J M Bovard4, N D Eves5, K A Gelmon6, D C McKenzie7, S A Virani8, E J Stöhr9, D E R Warburton10, K L Campbell11. 1. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: amy.kirkham@ubc.ca. 2. Cardiff Metropolitan University, Cyncoed Campus, Cyncoed Rd, Cardiff CF23 6XD, UK. Electronic address: rshave@cardiffmet.ac.uk. 3. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: kelcey.bland@ubc.ca. 4. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: joshbovard@gmail.com. 5. University of British Columbia Okanagan, 1147 Research Road, Kelowna, BC V1V 1V7, Canada. Electronic address: neil.eves@ubc.ca. 6. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada; British Columbia Cancer Agency, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. Electronic address: kgelmon@bccancer.bc.ca. 7. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: don.mckenzie@ubc.ca. 8. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: svirani@telus.net. 9. Cardiff Metropolitan University, Cyncoed Campus, Cyncoed Rd, Cardiff CF23 6XD, UK. Electronic address: estohr@cardiffmet.ac.uk. 10. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: darren.warburton@ubc.ca. 11. University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: kristin.campbell@ubc.ca.
Abstract
BACKGROUND: Preclinical studies have reported that a single treadmill session performed 24h 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 24h prior to treatment changes this response. METHODS:Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h 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 24-48h 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 24h 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.
RCT Entities:
BACKGROUND: Preclinical studies have reported that a single treadmill session performed 24h 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 24h prior to treatment changes this response. METHODS:Breast cancerpatients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h 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 24-48h 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 24h 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.
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