Cardiovascular Rehabilitation in Patients With Severe Aortic Stenosis Submitted to Valvar Correction

Study Overview
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Brief Summary
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This study will be evaluate the autonomic, endothelial and hemodynamic functions, inspiratory muscle strength, peripheral tissue oxygenation, peripheral and respiratory muscle architecture, and inflammatory profile of severe AS patients submitted undergoing to valve replacement (sAVR) or transcatheter aortic valve implantation (TAVI), and their influence on the pathophysiological mechanisms involved in cardiovascular rehabilitation.

Detailed Description
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Background: Aortic stenosis (AS) is a disease characterized by the inadequate valve opening, compromising the cardiac output. Surgical aortic valve replacement (sAVR) is the procedure indicates for valve repair in AS symptomatic cases whereas the transcatheter aortic valve implantation (TAVI) is the procedure indicates for sAVR contraindicated cases. Objective: To evaluate the effect of the cardiac rehabilitation program (pre-procedure, early post-procedure, and late post-procedure) in autonomic, endothelial and hemodynamic functions, inspiratory muscle strength, peripheral tissue oxygenation, peripheral and respiratory muscle architecture, and inflammatory profile of severe AS patients submitted to a valve repair procedure (sAVR or TAVI). Methods: The present study will be a randomized double-blind clinical trial in patients indicated to valve repair procedure. This research will be divided into four phases: phase 1 (pre-procedure); phase 2 (early post-procedure); phase 3 (late post-procedure) and phase 4 (follow-up). Phase 1: participants will be randomized in PR-I (pre-intervention) or PR-C (control). Pre-procedure rehabilitation program will consist of daily neuromuscular electrical stimulation (NMES) in knee extensor muscles and inspiratory muscle training (IMT) sessions. PR-C group will receive daily visits, but with a NMES + IMT protocols using a minimal load. Phase 2: a new random will be done between ER-II or ER-CI (intervention) and ER-IC or ER-CC (control). Intervention groups will undertake an early post-procedure rehabilitation (NMES in knee extensor muscle plus IMT for six weeks). Control groups will receive the same protocol using a minimal load without load progression. Phase 3: all patients will be referred to the conventional cardiac rehabilitation program (aerobic and resistance training) for 8-weeks. Phase 4: follow-up (no interventions), will be done after 3, 6, 9 and 12 months. Assessment protocol will be composed by cardiopulmonary exercise test, autonomic (heart rate variability), endothelial (flow-mediated vasodilation), hemodynamic function (cardiothoracic impedance) functional capacity (six-minute walk test), maximum inspiratory pressure, peripheral and respiratory muscle architecture (ultrasonography), and tissue oxygenation (near-infrared spectroscopy), and inflammatory profile (OxLDL, TGF-β, TNF-α, IL-1b, IL-10 and ICAM-1) Appropriate statistic tests will be used to compare the time-rehabilitation (experimental vs sham) and group-interaction (sAVR vs TAVI). If samples are abandoned or lost, basal data will be double entered to characterize the intention-to-treat analysis.

Official Title
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Cardiovascular RehAbilitation in Patients With Severe AoRtic StEnosis Submitted to Valvar Correction: Effects on Muscle Architecture, Tissue Oxygenation, EndoThelial Function, Inflammatory Profile, and AutoNomic Control - Randomized Trial

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Behavioral: cardiovascular rehabilitation program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients NYHA class II-IV who has not participated in a CRP three months before recruitment; older than 40 years; of both genders; with degenerative AS and indication for valve repair. The patients will not know which protocol to undergo. Exclusion Criteria: patients with low cognitive level to perform the assessment or intervention procedures; that exhibit unstable angina or any contraindications for the treatment or measurements; as well musculoskeletal, cerebrovascular, or psychiatric disease that prevents their participation in the research.

Ages Eligible for Study
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Minimum Age: 40 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
Interventional Model Description: This study will be divided into four phases: phase 1 (pre-procedure rehabilitation); phase 2 (early post-procedure rehabilitation); phase 3 (late post-procedure rehabilitation), and phase 4 (follow-up).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: aortic valve replacement<br>patients with aortic stenosis submitted to aortic valve replacement procedure | Behavioral: cardiovascular rehabilitation program<br>* Phase I: 2-weeks of respiratory muscle training and neuromuscular electrical stimulation (daily at hospital). Phase II: 6-weeks of respiratory muscle training and neuromuscular electrical stimulation (daily at home). Phase III: 8-weeks of supervised, structured, combined aerobic and resistance training.<br>|
| Experimental: transcatheter aortic valve implantation<br>patients with aortic stenosis who underwent to transcatheter aortic valve implantation | Behavioral: cardiovascular rehabilitation program<br>* Phase I: 2-weeks of respiratory muscle training and neuromuscular electrical stimulation (daily at hospital). Phase II: 6-weeks of respiratory muscle training and neuromuscular electrical stimulation (daily at home). Phase III: 8-weeks of supervised, structured, combined aerobic and resistance training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiorespiratory function | Peak oxygen consumption (VO2PEAK), among other physiologic markers. | Changes from 8 and 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Autonomic function | will be evaluated by heart rate variability using a wrist heart rate monitor following the recommendations of ESC/NASPE Task Force. | Change from 2, 8 and 16 weeks | 
| Endothelial function | will be investigated by endothelium-dependent flow-mediated vasodilation (FMD) technique following the International Brachial Artery Reactivity Task Force. | Changes from 2, 8 and 16 weeks | 
| Hemodynamic function | will be evaluated the cardiac output using a cardiothoracic impedance device (noninvasive approach). | Changes from 2, 8 and 16 weeks | 
| Inflammatory profile | Plasma levels will be determined by enzyme-linked immunosorbent assay using commercial systems. | Changes from 2, 8 and 16 weeks | 
| Inspiratory muscle strength | Will be assessed as maximum inspiratory pressure (MIP) using a digital device following recommendations of the American Thoracic Society and European Respiratory Society. | Changes from 2, 8 and 16 weeks | 
| Muscle architecture (peripheral muscles) | Will be evaluated the muscle thickness (cross-sectional area) of quadriceps using a ultrasonography system. | Changes from 8 and 16 weeks | 
| Muscle architecture (respiratory muscles) | Will be evaluated the diaphragm thickness (cross-sectional area) of quadriceps using a ultrasonography system. | Changes from 8 and 16 weeks | 
| Tissue oxygenation | near-infrared spectroscopy (NIRS) will be used to verify muscle oxygenation (quadriceps and respiratory muscles). | Changes from 2, 8 and 16 weeks | 
| Functional capacity | The patients under favorable clinical conditions will be functionally evaluated by the Six-Minute Walk Test (6MWT) according to current guidelines. | Changes from 8 and 16 weeks | 
| Mortality | to evaluate the survival rate of the patients | Change from 3, 6 and 12 months post protocol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic stenosis, aortic valve replacement, transcatheter aortic valve implantation, frailty, cardiac rehabilitation