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NCT Number: NCT07164911

Predictive Factors of Response to Phase II Cardiac Rehabilitation in Heart Failure With Reduced Ejection Fraction

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.

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Key information

Conditions

HFrEF - Heart Failure With Reduced Ejection Fraction Cardiac Rehabilitation Exercise Adaptations Exercise Intervention Exercise Intolerance Exercise Training

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital center of Corbie

Corbie, 80800, France

Location status: Recruiting

Location contact

Francesco Orlando, MD

PRINCIPAL_INVESTIGATOR

Pierre-Marie Leprêtre, PhD

CONTACT

[email protected]

33 322 964 120

About this study

Key Takeaways VO₂peak is a clinically relevant, prognostic measure in HFrEF. .ExCR benefits are heterogeneous, partly due to variable cardiac and muscular adaptations. c-miRNAs may mediate or indicate the molecular response to ExCR. c-miRNAs may Enhance pulmonary, cardiac, or muscular adaptations → improved VO₂peak, or, if maladaptive, contribute to fatigue → explaining non-response.

Goal Connect ΔVO₂peak with cellular precursors of adaptation, providing a mechanistic understanding of CR responses.

Method 62 patients with HFrEF will be engaged in a this prospective, single-center cohort follow-up study with a prognostic aim and minimal risk to human participants.

Peak values of oxygen uptake, cardiac hemodynamics, cerebral and muscle oxygenation, non-coding RNA will be measured before and after Exercise based cardiac rehabilitation during a cardiopulmonary exercise testing. All the patients will perform a force - velocity test in order to prescribe an individualized resistance training program.

Originality of study: Combines non-invasive physiological measurements during exercise and biomarker (c-miRNA) analysis before and after ExCR.

Scientific and Clinical Significance

Linking non-invasive measurements and epigenetic markers could:

  • Identify which component of the oxygen transport chain is most impaired.
  • Combining physiological and molecular assessments could guide tailored rehabilitation strategies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Prescription for phase II cardiac rehabilitation
  • BMI between 20-30 kg·m-²
  • Physical activity level: sedentary or physically active but untrained
  • Signed informed consent to participate in the study
  • Affiliation to the French national health insurance system

Exclusion criteria

  • Contraindication to regular adapted physical activity
  • Uncontrolled arterial hypertension
  • Secondary respiratory disease such as emphysema or chronic obstructive pulmonary disease (COPD)
  • Secondary cardiovascular disease
  • Individuals under legal protection or deprived of liberty
  • Pregnant or breastfeeding women

Treatment and study plan

Primary outcomes

  1. ΔVO₂peak

    Time frame: Day 1 : baseline value of peak oxygen consumption (preVO₂peak) Day 21: post value of peak oxygen consumption (post VO₂peak)

    Variation in peak oxygen consumption during exercise (ΔVO₂peak = postVO₂peak - preVO₂peak), expressed as the percentage change from baseline after exercise training.

  2. circulating microRNAs

    Time frame: Day 1 : baseline expression of miRNAs (pre-miRNAs) Day 21: post values of miRNAs expression (post-miRNAs)

    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

Secondary outcomes

  1. Changes in pulmonary ventilation

    Time frame: Day 1: pulmonary ventilation at baseline (preVE, L·min-¹) Day 21: post value of pulmonary ventilation (postVE, L·min-¹)

    Changes (pre-post exercise training) in pulmonary ventilation (VE, L·min-¹).

  2. Changes in alveolar ventilation with exercise training

    Time frame: Day 1: alveolar ventilation at baseline (postVA, mL·min-¹) Day 21: post value of alveolar ventilation (postVA, mL·min-¹)

    Changes (pre-post exercise training) in alveolar ventilation (VA, mL·min-¹)

  3. Changes in alveolar-arterial oxygen pressure difference with exercise training

    Time frame: Day 1: baseline alveolar-arterial oxygen pressure difference value (prePA-aO₂, mmHg) Day 21: post value of alveolar-arterial oxygen pressure difference (postPA-aO₂, mmHg)

    Changes (pre-post exercise training) in alveolar-arterial oxygen pressure difference (PA-aO₂, mmHg)

  4. Changes in cardiac index with exercise training

    Time frame: Day 1: baseline value of cardiac index (preCI, L·min-¹·m-²) Day 21: post value of cardiac index (postCI, L·min-¹·m-²)

    Changes (pre-post exercise training) in cardiac index (CI, L·min-¹·m-²)

  5. Changes in arterial stiffness with exercise training

    Time frame: Day 1: baseline value of arterial stiffness (prePWV, m·s-¹) Day 21: post value of arterial stiffness (postPWV, m·s-¹)

    Changes (pre-post exercise training) in arterial stiffness (PWV, m·s-¹)

  6. Changes in muscle oxygen saturation

    Time frame: Day 1: baseline value of muscle oxygen saturation (preSmO₂, %) Day 2: post value of muscle oxygen saturation (postSmO₂, %)

    Changes (pre-post exercise training) in muscle oxygen saturation (SmO₂, %)

  7. Changes in cerebral oxygen saturation with exercise training

    Time frame: Day 1: baseline value of cerebral oxygen saturation (%) Day 21: baseline value of cerebral oxygen saturation '%)

    Changes (pre-post exercise training) in cerebral oxygen saturation (%)

Study contacts

Contact information is provided by the study sponsor or research team.

Pierre-Marie Leprêtre, professor

CONTACT

[email protected]

+33235148113

Sponsors and collaborators

Lead sponsor

Centre Hospitalier de Corbie

Other Gov

Registry information

Official study title

Prédiction Des réponses du Patient Porteur d'Une Insuffisance Cardiaque à Fraction d'éjection altérée à Une Phase II de réadaptation Cardiaque

Acronym: PrédicRéa

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Sep 10, 2025
Registry last updated
Dec 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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