Exercise intolerance, measured as peak oxygen consumption (VO₂peak) during exercise in patients with heart failure with reduced ejection fraction (HFrEF). Change in VO₂peak (ΔVO₂peak), which serves as a prognostic marker for HFrEF engaged in exercise based cardiac rehabilitation program (ExCR). Responders to ExCR generally show improved cardiac function but some patients with HFrEF do not respond to ExCR. VO₂peak depends on three major components of oxygen transport: Pulmonary (lungs), circulatory (heart and vessels) and skeletal muscle (oxygen utilization) functions. These physiological responses to ExCR may be influenced by epigenetic regulation, specifically the expression of circulating microRNAs (c-miRNAs).
Linking non-invasive measurements and epigenetic markers could 1) identify which component of the oxygen transport chain is most impaired and 2) allow personalized interventions to maximize VO₂peak improvements.
The primary objective of this stidy is to assess the association between changes in VO₂peak during exercise training and circulating microRNA expression (miR-146a, miR-191, miR-23a, miR-140, miR-1, miR-21, miR-133a, miR-17-5p, miR-3200-3p).
The secondary objective is to examine the relationship between pulmonary, cardiovascular, and neuromuscular adaptations to exercise and circulating microRNA expression.
Heart failure with reduced ejection fraction < 40%
NYHA functional class ≥ II
Clinically stable for at least 6 weeks
On optimized medical therapy for at least 6 weeks
Contraindication to regular adapted physical activity
Uncontrolled arterial hypertension
Secondary respiratory disease such as emphysema or chronic obstructive pulmonary disease (COPD)
Secondary cardiovascular disease
Heart failure patient with altered left ventricular ejection fraction
Cohort
Prospective
Not listed
ΔVO₂peak
Variation in peak oxygen consumption during exercise (ΔVO₂peak = postVO₂peak - preVO₂peak), expressed as the percentage change from baseline after exercise training.
circulating microRNAs
Expression of circulating microRNAs (c-miRNAs): miR-146a, miR-191, miR-23a, miR-140, miR-1, miR-21, miR-133a, miR-17-5p, miR-3200-3p
Changes in pulmonary ventilation
Changes (pre-post exercise training) in pulmonary ventilation (VE, L·min-¹).
Changes in alveolar ventilation with exercise training
Changes (pre-post exercise training) in alveolar ventilation (VA, mL·min-¹)
Changes in alveolar-arterial oxygen pressure difference with exercise training
Changes (pre-post exercise training) in alveolar-arterial oxygen pressure difference (PA-aO₂, mmHg)
Changes in cardiac index with exercise training
Changes (pre-post exercise training) in cardiac index (CI, L·min-¹·m-²)
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