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

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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 ( IF 8.4 ) Pub Date : 2021-12-29 , DOI: 10.1093/eurjpc/zwab151
Andreas B Gevaert _{1,

2} , Isabel Witvrouwen _{1,

2} , Amaryllis H Van Craenenbroeck _{3,

4} , Steven J Van Laere ₅ , Jente R A Boen _{1,

6} , Caroline M Van de Heyning _{1,

2} , Evgeny Belyavskiy _{7,

8} , Stephan Mueller _{9,

10} , Ephraim Winzer ₁₁ , André Duvinage _{9,

10} , Frank Edelmann _{7,

8} , Paul J Beckers ₂ , Hein Heidbuchel _{1,

2} , Ulrik Wisløff ₁₂ , Burkert Pieske _{7,

8} , Volker Adams ₁₁ , Martin Halle _{9,

10} , Emeline M Van Craenenbroeck _{1,

2} ,

Affiliation

Research Group Cardiovascular Diseases, GENCOR Department, University of Antwerp, Campus Drie Eiken D.T.228, Universiteitsplein 1, 2610 Antwerp, Belgium.
Department of Cardiology, Antwerp University Hospital (UZA), Edegem, Belgium.
Research Group Nephrology and Renal Transplantation, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
Translational Cancer Research Unit, Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium.
Research Group Physiopharmacology, GENCOR Department, University of Antwerp, Antwerp, Belgium.
Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany.
DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany.
Department of Prevention and Sports Medicine, University Hospital Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Heart Center Dresden - University Hospital, Department of Internal Medicine and Cardiology, Technische Universität Dresden, Dresden, Germany.
Cardiac Exercise Research Group at Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

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.

更新日期：2021-09-11

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