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NCT Number: NCT05726474

Comparison of the Effect of Two Types of Physical Exercises in Patients With Heart Failure With Preserved Ejection Fraction

Background: Heart failure (HF) is a chronic disease with a very important and increasingly severe social and health impact with a prevalence of 6.8% in Spain. HF with preserved ejection fraction (HFpEF) represents approximately 50% of all patients with HF. In the absence of pharmacological treatments that have succeeded in reducing mortality or morbidity in this pathology, it is recommended that interventions be directed at prevention, symptomatic treatment of HF and treatment of comorbidities to avoid exacerbations, thus physical exercise is recognized as an important adjunct in the treatment of HF and is recommended by the guidelines of the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC). Currently, aerobic exercise is the most studied physical exercise in this population, but in recent years high-intensity interval training (HIIT) and the combination of aerobic exercise with strength training (combined exercise) have emerged.

Objectives: The overall objective of this study is to compare the effectiveness of combined training and HIIT on exercise capacity, diastolic function, endothelial function, and arterial stiffness in patients with HFpEF. The specific objectives of this study are: a) to compare the effectiveness of combined training and HIIT on quality of life in patients with HFpEF and b) to analyze the cost-effectiveness of combined training and HIIT versus conventional treatment in patients with HFpEF.

Methodology: The ExIC-FEp study will be a single-blind randomized clinical trial with 3 arms (combined exercise, HIIT and a control group), conducted at the Health and Social Research Center of the University of Castilla-La Mancha, to analyze two types of supervised physical exercise in patients with HFpEF for 6 months. Patients with HFpEF will be randomly assigned (1:1:1) to the combined exercise, HIIT or control group. All participants will be examined, at baseline (prior to randomization), at three months (mid-intervention) and at six months (at the end of the intervention). Participants will undergo physical examination, echocardiography, maximal cardiopulmonary stress test, and measurement of endothelial function and arterial stiffness. In addition, sociodemographic variables, quality of life, physical activity, adherence to the Mediterranean diet, strength, spirometry and blood sampling will be measured.

Expected scientific contributions: this randomized clinical trial will represent a a significant advance in the scientific evidence available on the efficacy of physical exercise in the treatment of HFpEF, through: (a) transfer of the results to physicians, nurses and patients; (b) dissemination of results through scientific articles, doctoral theses and participation in congresses; (c) press releases and press conferences with the aim of disseminating the research results to the population; (d) dissemination through social networks to improve the social impact; and (e) design and content development of a web page.

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Key information

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Universidad de Castulla-La Mancha

Cuenca, 16001, Spain

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Heart Failure with preserved ejection fraction picture (diagnosis according to ESC 2021 criteria)
  • Signs and symptoms of Heart Failure
  • A left ventricular ejection fraction of ≥50%.
  • Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of left ventricular diastolic dysfunction/elevated left ventricular filling pressures, including elevated natriuretic peptides.
  • Sedentary men and women (structured exercise <2 x 30 min/week).
  • Age ≥40 years
  • Written informed consent
  • Clinically stable for 6 weeks
  • Optimal medical treatment for ≥6 weeks

Exclusion criteria

  • Non-cardiac causes of heart failure symptoms:
  • Significant valvular or coronary artery disease - Uncontrolled hypertension or arrhythmias.
  • Primary cardiomyopathies
  • Significant pulmonary disease (FEV1<50% predicted, GOLD III-IV)
  • Inability to exercise or conditions that may interfere with exercise intervention.
  • Myocardial infarction in the last 3 months
  • Signs of ischaemia during maximal cardiopulmonary exercise test.
  • Comorbidity that may influence one-year prognosis 7. Participation in another clinical trial.

Treatment and study plan

Combined Exercise

Behavioral

Patients will exercise for 40 minutes three times a week on an ergometric bicycle at 50-60% of VO2max, 60-70% of HRmax, 11-13 on the Borg scale, without ergometer at 50-60% of VO2max, 60-70% of HRmax, 11-13 on the Borg scale, without shortness of breathing difficulty. In addition, strength training will be performed (bench press, leg press, leg curl, leg machine, bench press, leg press, leg curl, leg curl, leg machine). leg curls, leg curls, rowing machine, triceps dips, pectoral pull-ups) twice a week. week. Strength training will be performed with 15 repetitions per exercise and per session, with a corresponding workload of 15 repetitions. session, with a workload corresponding to 60% to 65% of the 1-repetition maximum (1RM) measured at (1RM) measured at the beginning and at the end of the intervention.

High interval training

Behavioral

Patients will perform three training sessions per week. Each training session begins with a 10-minute warm-up at moderate intensity (corresponding to 50-60% of VO2max, 60-70% of HRmax, 11-13 on the Borg scale, no shortness of breath) before cycling, four 4-minute intervals at high intensity (corresponding to 85-90% of VO2max, 90-95% of HRmax, 15-17 on the Borg scale, shortness of breath). Each interval will be separated by 3 minutes of active pauses, with a HRmax of 50-70%. The training session will end with 3 minutes of cool down at moderate intensity (corresponding to 50-60%). moderate intensity (corresponding to 50-60% of VO2max, 60-70% of HRmax, 11-13 on the Borg scale, without difficulty). Borg scale, no shortness of breath). The total exercise time will be 40 minutes for the HIIT group.

Primary outcomes

  1. Exercise capacity

    Time frame: Change from Baseline exercise capacity at 3 months

    Maximal cardiopulmonary stress test with Ergoline600 ergometer bicycle.

  2. E velocity

    Time frame: Change from Baseline E velocity at 3 months

    E velocity in m/s

  3. Endothelial function

    Time frame: Change from Baseline endothelial function at 3 months

    Carotid intima-media thickness: by ultrasound with the Sonosite SII device.

  4. Arterial stiffness

    Time frame: Change from Baseline arterial stiffness at 3 months

    Pulse wave velocity and augmentation index

  5. A velocity

    Time frame: Change from Baseline A velocity at 3 months

    A velocity in m/s

  6. E/A ratio

    Time frame: Change from Baseline E/A ratio at 3 months

    E/A ratio

  7. e' velocity

    Time frame: Change from Baseline e' velocity in m/s at 3 months

    e' velocity in m/s

  8. E/e' ratio

    Time frame: Change from Baseline E/e' ratio at 3 months

    E/e' ratio

  9. ejection fraction

    Time frame: Change from Baseline ejection fraction at 3 months

    percentage of ejection fraction

  10. left ventricular volume index

    Time frame: Change from Baseline left ventricular volume index at 3 months

    left ventricular volume index

  11. end-diastolic volume

    Time frame: Change from Baseline end-diastolic volume at 3 months

    end-diastolic volume

  12. left ventricular mass

    Time frame: Change from Baseline left ventricular mass at 3 months

    left ventricular mass

  13. left atrial diameter

    Time frame: Change from Baseline left atrial diameter at 3 months

    left atrial diameter

  14. isovolume relaxation time

    Time frame: Change from Baseline isovolume relaxation time at 3 months

    isovolume relaxation time in seg

  15. deceleration time

    Time frame: Change from Baseline deceleration time at 3 months

    deceleration time in m/s

  16. left atrial volume index

    Time frame: Change from Baseline left atrial volume index at 3 months

    left atrial volume index

Secondary outcomes

  1. Sociodemographic variables

    Time frame: Baseline

    Age, sex and socioeconomic level

  2. Patient's medical history

    Time frame: Baseline

    Comorbidities and medication

  3. Weight

    Time frame: Change from Baseline weight at 3 months

    Weight in kilogram

  4. Muscular strength

    Time frame: Change from Baseline Muscular strength at 3 months

    Handgrip force to be determined with TKK 5401 Grip-D dynamometer.

  5. Spirometry

    Time frame: Change from Baseline spirometry at 3 months

    Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and FEV1/FVC ratio.

  6. Glucose

    Time frame: Change from Baseline Glucose at 3 months

    Glucose

  7. Physical activity

    Time frame: Change from Baseline phisical activity at 3 months

    Accelerometry. Time of physical activity

  8. HQoL

    Time frame: Change from Baseline HQoL at 3 months

    Validated 12-item health questionnaire (SF-12). From 0 to 12 (higher values better HQoL)

  9. Adherence to the Mediterranean diet

    Time frame: Change from Baseline Adherence to the Mediterranean diet at 3 months

    Validated 14-item questionnaire on adherence to the Mediterranean diet (MEDAS-14). From 0 to 14 (higher values better Adherence)

  10. height

    Time frame: Change from Baseline height at 3 months

    height in centimeters

  11. BMI

    Time frame: Change from Baseline BMI at 3 months

    BMI in kg/m2

  12. waist circumference

    Time frame: Change from Baseline waist circumference at 3 months

    waist circumference in cm

  13. body fat

    Time frame: Change from Baseline body fat at 3 months

    percentage of body fat

  14. blood pressure

    Time frame: Change from Baseline blood pressure at 3 months

    systolic and diastolic blood pressure in mmHg

  15. total cholesterol

    Time frame: Change from Baseline total cholesterol at 6 months

    total cholesterol

  16. triglycerides

    Time frame: Change from Baseline triglycerides at 6 months

    triglycerides

  17. HDL-cholesterol

    Time frame: Change from Baseline HDL-cholesterol at 6 months

    HDL-cholesterol

  18. LDL-cholesterol

    Time frame: Change from Baseline LDL-cholesterol at 6 months

    LDL-cholesterol

  19. apolipoproteins A1 and B

    Time frame: Change from Baseline apolipoproteins A1 and B at 6 months

    apolipoproteins A1 and B

  20. insulin

    Time frame: Change from Baseline insulin at 6 months

    insulin

  21. ultra-sensitive C-reactive protein

    Time frame: Change from Baseline ultra-sensitive C-reactive protein at 6 months

    ultra-sensitive C-reactive protein

  22. N-terminal pro-B-type natriuretic peptide (NT-proBNP)

    Time frame: Change from Baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 6 months

    N-terminal pro-B-type natriuretic peptide (NT-proBNP)

  23. HbA1c

    Time frame: Change from Baseline HbA1c at 6 months

    HbA1c

Sponsors and collaborators

Lead sponsor

University of Castilla-La Mancha

Other

Registry information

Official study title

Comparison of the Effect of Two Types of Physical Exercise on the Improvement of Exercise Capacity, Diastolic Function, Endothelial Function, and Arterial Stiffness in Patients With Heart Failure With Preserved Ejection Fraction (ExIC-FEp Study)

Acronym: ExIC-FEp

Important dates

Study start
2023
Primary completion
2024
Study completion
2025
First posted
Feb 14, 2023
Registry last updated
Jun 4, 2025

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

View the official ClinicalTrials.gov record (opens in a new tab)

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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