Impact of Interval Training on Sympathetic Hyperactivity and Vascular Function

Study Overview
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Brief Summary
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In this study, the investigators are testing the hypothesis that reduction in sympathetic activity would be greater following high-intensity interval training (HIIT) than moderate-intensity continuous training (MICT) and correspond with improvements in peripheral vascular function, and skeletal muscle function in patients with heart failure with reduced ejection fraction (HFrEF).

Detailed Description
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In this study, the investigators are testing the hypothesis that reductions in sympathetic activity would be greater following high-intensity interval training (HIIT) than moderate-intensity continuous training (MICT) and correspond with improvements in peripheral vascular function, and skeletal muscle function in patients with heart failure with reduced ejection fraction (HFrEF). To test this hypothesis patients with chronic heart failure (30 - 65 years), left ventricular ejection fraction ≤40%, Functional Classes II-III), are being randomized into exercise with HIIT, MICT or no training (NT) three times/week for 12 weeks. Muscle sympathetic nerve activity is assessed by microneurography. Brachial artery flow-mediated dilation (FMD), blood flow and vascular conductance were assessed by ultrasonography. Blood pressure (BP) and heart rate (HR) by are being measured via finger photoplethysmograph and peak oxygen uptake (V̇O2peak) by a cardiopulmonary exercise test on ergometer cycle for leg. Biopsy samples from the lateral vast of the thigh are being collected for analysis of the intracellular mechanisms in the skeletal muscle. Exercise training is being conducted under supervision at the Heart Institute, School of Medicine, University of São Paulo. Both HIIT and MICT are performed on a cycle ergometer, three times per week for 12 weeks, and training sessions were matched for energy expenditure (i.e., an isocaloric energy expenditure of 200 Kcal/session). The intensity of the MICT session is established based on the HR and workload levels corresponding to anaerobic threshold and respiratory compensation point (RCP). The intensity of the HIIT session is established based on the HR and workload levels corresponding to 5% above the RCP. All exercise sessions were performed under the supervision of an exercise physiologist. The patients in the NT group were instructed to avoid any regular exercise program or any non-supervised exercise protocol during the study. All patients are being assessed before (pre) and after (post) both exercise training modes or control, no training.

Official Title
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The Impact of High-intensity Interval Training Versus Moderate Continuous Training on Neurovascular Control in Patients With Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Exercise training of High Intensity
* Other: Exercise training of Moderate Intensity
* Other: Untraining


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Functional Class II to III of New York Heart Association Left ventricular ejection fraction ≤40% Peak oxygen uptake (V̇O2) <20 ml•kg-1•min-1 Exclusion Criteria: Myocardial infarction within three months Unstable angina Acute heart failure Pacemaker Pulmonary disease Chronic renal disease Peripheral neuropathy History of stroke Untreated hypo/hyperthyroidism Body mass index (BMI) >30 kg/m2 History of smoking

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-intensity interval training (HIIT)<br>High-intensity interval training (HIIT) = the exercise of high intensity perform on a cycle ergometer, three times per week for 12 weeks, and training sessions were matched for energy expenditure (i.e., an isocaloric energy expenditure of 200 Kcal/session). The intensity of the HIIT session was established based on the HR and workload levels corresponding to 5% above the respiratory compensation point. | Other: Exercise training of High Intensity<br>* High intensity<br>* Other names: Physical exercise;|
| Experimental: Moderate-intensity continuous training (MICT)<br>Moderate-intensity continuous training (MICT) = the exercise of moderate intensity perform on a cycle ergometer, three times per week for 12 weeks, and training sessions were matched for energy expenditure (i.e., an isocaloric energy expenditure of 200 Kcal/session). The intensity of the MICT session was established based on the HR and workload levels corresponding to anaerobic threshold and respiratory compensation point | Other: Exercise training of Moderate Intensity<br>* Moderate intensity<br>|
| Sham Comparator: No training<br>The patients are instructed to avoid any regular exercise program or any non-supervised exercise protocol during the study. | Other: Untraining<br>* Sedentary<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle sympathetic nerve activity (MSNA) | MSNA is being assessed by microneurography | Baseline and 12 weeks | 
| Change muscle mechanoreceptor sensitivity | The mechanoreceptor sensitivity is being assessed via passive exercise to the leg | Baseline and 12 weeks | 
| Change muscle metaboreceptor sensitivity | The metaboreceptor sensitivity is being assessed via dynamic exercise to the leg.The exercise intensity is 30% maximum voluntary contraction. | Baseline and 12 weeks | 
| Change in chemoreceptor sensitivity | Hypoxia via 10% oxygen | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral vascular function | Brachial artery flow-mediated dilation is being used to assess the vascular function | Baseline and 12 weeks | 
| Skeletal muscle function | The skeletal muscle function is being assessed in biopsy samples collected in lateral vasts of thigh with needle of biopsy. | Baseline and 12 weeks |