Circulating microRNA as predictors for exercise response in heart failure with reduced ejection fraction

Area of Science:

• Cardiology
• Genetics
• Exercise Physiology

Background:

• Exercise training improves cardiorespiratory fitness in heart failure with reduced ejection fraction (HFrEF).
• Approximately 55% of HFrEF patients do not achieve significant improvements in peak oxygen uptake (VO2peak) with exercise.
• MicroRNAs (miRNAs) are epigenetic regulators that may influence VO2peak trainability.

Purpose of the Study:

• To investigate if circulating miRNAs can differentiate exercise responders (ER) from non-responders (ENR) in HFrEF patients.
• To identify specific miRNAs associated with VO2peak improvement after exercise training.
• To explore the potential of miRNAs for predicting exercise response in HFrEF.

Main Methods:

• Analysis of 377 miRNAs in 18 male HFrEF patients (9 ER, 9 ENR) before 15 weeks of exercise training.
• Unsupervised clustering and differential expression analysis of miRNAs.
• Gene set enrichment analysis to identify targeted pathways.

Main Results:

• Unsupervised miRNA clustering accurately distinguished ER from ENR (83% accuracy).
• 57 miRNAs were differentially expressed between ER and ENR.
• A panel of seven upregulated miRNAs in ENR predicted non-response with an area under the curve ≥0.77.

Conclusions:

• A specific miRNA signature is strongly correlated with VO2peak trainability in HFrEF.
• This miRNA fingerprint shows potential for predicting exercise training response.
• Findings may facilitate personalized exercise prescriptions for HFrEF patients.