Cardiovascular Rehabilitation in Patients With Severe Aortic Stenosis Submitted to Valvar Correction (CARE-AS-MOTION)

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

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.

Study Overview

• Status: Unknown
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Behavioral: cardiovascular rehabilitation program

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marlus Karsten, PhD; Phone Number: 55 51 33038876; Email: mkarsten@ufcspa.edu.br

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
      • Marlus Karsten
      • Contact: Marlus Karsten, PhD; Phone Number: +55 51 33038876; Email: mkarsten@ufcspa.edu.br
      • Contact: Gustavo S Ribeiro; Phone Number: +55 51 99848530; Email: gustavosr@ufcspa.edu.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: aortic valve replacement; patients with aortic stenosis submitted to aortic valve replacement procedure	Behavioral: cardiovascular rehabilitation program; 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.
Experimental: transcatheter aortic valve implantation; patients with aortic stenosis who underwent to transcatheter aortic valve implantation	Behavioral: cardiovascular rehabilitation program; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Irmandade Santa Casa de Misericórdia de Porto Alegre
• Collaborators: Federal University of Health Science of Porto Alegre
• Investigators: Principal Investigator: Marlus Karsten, PhD, Federal University of Health Science of Porto Alegre

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2020
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: May 21, 2015
• First Submitted That Met QC Criteria: June 5, 2015
• First Posted (Estimate): June 10, 2015

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: frailty; aortic valve replacement; aortic stenosis; transcatheter aortic valve implantation; cardiac rehabilitation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: IR00002509/FWA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No