Exercise Intervention in Patients With Heart Failure With Preserved and Reduced Ejection Fraction

Study Overview
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Brief Summary
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The objective of this study is to assess by what physiological mechanisms patients with heart failure benefit from exercise. Effects of an exercise intervention will be assessed for both central (heart and lungs) and peripheral (muscle fiber and mitochondria) factors.

Detailed Description
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A randomized, non-blinded prospective intervention trial. Patients randomized to exercise intervention will undergo supervised aerobic training on ergometer cycle for 12 weeks whilst control group receives standard care. Before and after the intervention, all participants will undergo cardiac magnetic resonance imaging (cardiac MR) examinations, Ventilation/Perfusion Single Photon Emission Computed Tomography (V/P SPECT), Cardiopulmonary exercise tests, muscle biopsies and blood sampling.

Official Title
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Physiological Mechanisms Affecting Exercise Capacity in Patients With Heart Failure - an Exercise Intervention Study Evaluated With Several Modalities

Conditions
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Heart Failure New York Heart Association (NYHA) Class III, Heart Failure New York Heart Association (NYHA) Class II

Intervention / Treatment
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* Other: Supervised Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signs and symptoms of heart failure Age ≥50 years Stable chronic heart failure (no hospitalizations within past month, no new medications past month) Able to understand and follow exercise prescription Currently physically inactive (less than 150 minutes/week moderate intensity exercise) Exclusion criteria: Currently or within the past 6 months been involved in cardiac rehab with exercise Devices or implants not compatible with magnetic resonance imaging or exercise testing Any orthopedic or medical condition affecting participation in testing and training Signs of acute ischemia during baseline cardiopulmonary exercise testing Participation in other clinical trials that may affect results Moderate or severe valvular disease Atrial fibrillation Moderate or severe chronic obstructive pulmonary disease NYHA class IV

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supervised exercise<br>The exercise intervention will include 2 supervised sessions of ergometer cycling with a warm up period of 10 minutes and 20 minutes of cycling at the aerobic intensity below the anaerobic threshold as determined from baseline results. Patients in the exercise arm will have 1 unsupervised exercise session where the participants walk or bicycle for 30 minutes at an intensity experienced as somewhat hard (Borg 13) according to the Borg Rating of Perceived Exertion Scale. | Other: Supervised Exercise<br>* 12 weeks of supervised aerobic exercise individually adapted to exercise capacity according to a VO2 peak test<br>|
| No Intervention: Standard of Care<br>The control group will receive advise to continue to live as usual. After 4 and 8 weeks, participants in the control group will be contacted by telephone for inquiry of general wellbeing. No other interventions will be performed in the control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal oxygen uptake (VO2peak) | a change in maximal oxygen uptake (VO2 peak) of 2 ml/min/kg | 12 weeks intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health related quality of life | Change in Health related quality of life assessed with Kansas City Cardiomyopathy Questionnaire (KCCQ). KCCQ scores are scaled from 0 to 100 and summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. | 12 weeks intervention | 
| Cardiac volumes and function | Change in cardiac volumes and function assessed using Cardiac MR indicating effects of the exercise intervention as compared to the control group | 12 weeks intervention | 
| Perfusion gradients on Ventilation / Perfusion Single Photon Emission Computed Tomography (V/P SPECT) | Change in pulmonary congestion quantified by V/P SPECT | 12 weeks intervention | 
| Mitochondrial function | Change in mitochondrial number and function using respirometry indicating effects of the exercise intervention as compared to the control group | 12 weeks intervention |