TY - JOUR
T1 - Efficacy of physical exercise to offset anthracycline-induced cardiotoxicity
T2 - A systematic review and meta-analysis of clinical and preclinical studies
AU - Naaktgeboren, Willeke R.
AU - Binyam, David
AU - Stuiver, Martijn M.
AU - Aaronson, Neil K.
AU - Teske, Arco J.
AU - van Harten, Wim H.
AU - Groen, Wim G.
AU - May, Anne M.
N1 - With supplementary file. Sources of Funding: This work was supported by the Dutch Cancer Society (KWF/Alpe,10325/2016-1).
PY - 2021/9/7
Y1 - 2021/9/7
N2 - BACKGROUND: Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. METHODS AND RESULTS: We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane’s and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. CONCLUSIONS: Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer.
AB - BACKGROUND: Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. METHODS AND RESULTS: We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane’s and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. CONCLUSIONS: Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer.
KW - Animals
KW - Antibiotics, Antineoplastic/adverse effects
KW - Cardiotoxicity/prevention & control
KW - Doxorubicin/adverse effects
KW - Exercise
KW - Humans
KW - anthracyclines
KW - cardiotoxicity
KW - meta-analysis
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85116172248&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34472371
UR - https://pure.hva.nl/ws/files/18653218/Supplemental_Material.pdf
UR - http://www.scopus.com/inward/record.url?scp=85116172248&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/JAHA.121.021580
DO - https://doi.org/10.1161/JAHA.121.021580
M3 - Article
C2 - 34472371
SN - 2047-9980
VL - 10
SP - 1
EP - 23
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 17
M1 - e021580
ER -