MiR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: An analysis of the OptimEx-Clin trial
Gevaert AB, Witvrouwen I, Van Craenenbroeck AH, Van Laere SJ, Boen JRA, Van De Heyning CM, Belyavskiy E, Mueller S, Winzer E, Duvinage A, Edelmann F, Beckers PJ, Heidbuchel H, Wisloff U, Pieske B, Adams V, Halle M, Van Craenenbroeck EM (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 28
Pages Range: 1722-1733
Journal Issue: 15
Abstract
Aims: In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients. Methods and results: We selected HFpEF patients from the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx) study which attended ≥70% of training sessions during 3 months (n = 51). Patients were defined as HR with a change in peakV·O2 above median (6.4%), and LR as below median (n = 30 and n = 21, respectively). Clinical, ergospirometric, and echocardiographic characteristics were similar between LR and HR. We performed an miRNA array (n = 377 miRNAs) in 14 age-and sex-matched patients. A total of 10 miRNAs were upregulated in LR, of which 4 correlated with peakV·O2. Validation in the remaining 37 patients indicated that high miR-181c predicted reduced peakV·O2 response (multiple linear regression, β =-2.60, P = 0.011), and LR status (multiple logistic regression, odds ratio = 0.48, P = 0.010), independent of age, sex, body mass index, and resting heart rate. Furthermore, miR-181c decreased in LR after exercise training (P-group = 0.030, P-time = 0.048, P-interaction = 0.037). An in silico pathway analysis identified several downstream targets involved in exercise adaptation. Conclusions: Circulating miR-181c is a marker of the response to exercise training in HFpEF patients. High miR-181c levels can aid in identifying LR prior to training, providing the possibility for individualized management.
Involved external institutions
University of Antwerp / Universiteit Antwerpen
Belgium (BE)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Technische Universität Dresden
Germany (DE)
Antwerp University Hospital (UZA)
Belgium (BE)
NTNU Trondheim - Norwegian University of Science and Technology
Norway (NO)
Belgium (BE)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Technische Universität Dresden
Germany (DE)
Antwerp University Hospital (UZA)
Belgium (BE)
NTNU Trondheim - Norwegian University of Science and Technology
Norway (NO)
How to cite
APA:
Gevaert, A.B., Witvrouwen, I., Van Craenenbroeck, A.H., Van Laere, S.J., Boen, J.R.A., Van De Heyning, C.M.,... Van Craenenbroeck, E.M. (2021). MiR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: An analysis of the OptimEx-Clin trial. European Journal of Preventive Cardiology, 28(15), 1722-1733. https://doi.org/10.1093/eurjpc/zwab151
MLA:
Gevaert, Andreas B., et al. "MiR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: An analysis of the OptimEx-Clin trial." European Journal of Preventive Cardiology 28.15 (2021): 1722-1733.
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