Clinical trial NCT02468219: Cardiovascular Rehabilitation in Patients With Severe Aortic Stenosis Submitted to Valvar Correction
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: aortic stenosis
aortic valve replacement
transcatheter aortic valve implantation
frailty
cardiac rehabilitation
Lead sponsor: Irmandade Santa Casa de Misericórdia de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Federal University of Health Science of Porto Alegre
First posted: 2015-06-10
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cardiorespiratory function
timeFrame: Changes from 8 and 16 weeks
Secondary outcomes:
measure: Autonomic function
timeFrame: Change from 2, 8 and 16 weeks
measure: Endothelial function
timeFrame: Changes from 2, 8 and 16 weeks
measure: Hemodynamic function
timeFrame: Changes from 2, 8 and 16 weeks
measure: Inflammatory profile
timeFrame: Changes from 2, 8 and 16 weeks
measure: Inspiratory muscle strength
timeFrame: Changes from 2, 8 and 16 weeks
measure: Muscle architecture (peripheral muscles)
timeFrame: Changes from 8 and 16 weeks
measure: Muscle architecture (respiratory muscles)
timeFrame: Changes from 8 and 16 weeks
measure: Tissue oxygenation
timeFrame: Changes from 2, 8 and 16 weeks
measure: Functional capacity
timeFrame: Changes from 8 and 16 weeks
measure: Mortality
timeFrame: Change from 3, 6 and 12 months post protocol
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Marlus Karsten
state: Rio Grande Do Sul
Study officials:
affiliation: Federal University of Health Science of Porto Alegre
name: Marlus Karsten, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Montemezzo D, Fregonezi GA, Pereira DA, Britto RR, Reid WD. Influence of inspiratory muscle weakness on inspiratory muscle training responses in chronic heart failure patients: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014 Jul;95(7):1398-407. doi: 10.1016/j.apmr.2014.02.022. Epub 2014 Mar 13.
citation: Russo N, Compostella L, Tarantini G, Setzu T, Napodano M, Bottio T, D'Onofrio A, Isabella G, Gerosa G, Iliceto S, Bellotto F. Cardiac rehabilitation after transcatheter versus surgical prosthetic valve implantation for aortic stenosis in the elderly. Eur J Prev Cardiol. 2014 Nov;21(11):1341-8. doi: 10.1177/2047487313494029. Epub 2013 Jun 11.
citation: Voller H, Salzwedel A, Nitardy A, Buhlert H, Treszl A, Wegscheider K. Effect of cardiac rehabilitation on functional and emotional status in patients after transcatheter aortic-valve implantation. Eur J Prev Cardiol. 2015 May;22(5):568-74. doi: 10.1177/2047487314526072. Epub 2014 Feb 27.
citation: Fauchere I, Weber D, Maier W, Altwegg L, Luscher TF, Grunenfelder J, Nowak A, Tuller D, Genoni M, Falk V, Hermann M. Rehabilitation after TAVI compared to surgical aortic valve replacement. Int J Cardiol. 2014 May 15;173(3):564-6. doi: 10.1016/j.ijcard.2014.03.121. Epub 2014 Mar 21. No abstract available.
citation: Sbruzzi G, Ribeiro RA, Schaan BD, Signori LU, Silva AM, Irigoyen MC, Plentz RD. Functional electrical stimulation in the treatment of patients with chronic heart failure: a meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil. 2010 Jun;17(3):254-60. doi: 10.1097/HJR.0b013e328339b5a2.