Cardiovascular, Pulmonary and Skeletal Muscle Evaluation Postoperative in Fontan Patients: Effects of Exercise Training

December 3, 2022 updated by: Aida Luiza R Turquetto, University of Sao Paulo

Cardiovascular, Pulmonary and Skeletal Muscle Evaluation in Patients With Univentricular Physiology in the Late Postoperative Period of the Fontan Surgery: Effects of Exercise Training

Introduction: The Fontan operation is the surgical treatment in most patients with either anatomic or functional single ventricles. In this operation, the subpulmonary ventricle is bypassed, connecting the systemic veins directly to the pulmonary arteries. The lack of a subpulmonary ventricle is associated with a nonpulsatile pulmonary flow and triggers a sequence of adaptive mechanisms along the life of these patients. The most frequent consequence of these adaptative mechanisms is the reduction in functional capacity, objectively measured by the decrease in peak oxygen consumption (VO2). So, cardiovascular and pulmonary functioning and skeletal muscle alterations can explain exercise intolerance in these patients.

Objectives: 1. To compare the cardiovascular, pulmonary, and musculoskeletal system variables in clinically stable Fontan patients with Healthy subjects; 2. To correlate the variables of the cardiovascular, pulmonary, and skeletal muscle with the functional capacity in Fontan patients; 3. To identify predictors of low functional capacity in this population; 4. To evaluate four-month aerobic exercise and inspiratory muscle training on functional capacity, pulmonary function, and autonomic control in patients after Fontan operation and compare to the group with no exercise training.

Methods: All subjects were submitted to cardiovascular, pulmonary, and skeletal muscle evaluation at baseline to perform a cross-sectional study comparing Fontan Patients (FP) with Healthy Controls (HC). In addition, the FP accepted to participate in the longitudinal clinical trial to evaluate exercise programs were randomized into three groups: Aerobic Exercise Training (AET), Inspiratory Muscle Training (IMT), and Non-exercise Training Group (NET, a control group). All patient groups (AET, IMT, NET) were reassessed after four months of training or under usual care.

Expected Outcomes: This study expects to demonstrate that impaired pulmonary function, altered neurovascular control, and reduced skeletal muscle could be an additional potential mechanism for reducing functional capacity in clinically stable Fontan patients. And this impairment could be diminished by exercise training, enhancing physical capacity, and exercise tolerance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

All subjects were submitted to cardiovascular magnetic resonance, echocardiography, cardiopulmonary exercise test, complete lung function, catecholamine and B-type natriuretic peptide (BNP) plasmatic levels, microneurography, venous occlusion plethysmography, six-minute walk test, phosphorus magnetic resonance spectroscopy (31P MRS) and magnetic resonance imaging (MRI) of skeletal muscle and quality of life (QoL) using the Short Form Health Survey (SF36) in the baseline. Comparative analyzes of the different systems of the two groups were done as well as tests to identify the predictors of low functional capacity in Fontan groups (FG).

The evaluation was done at baseline in healthy subjects. And in the Fontan group at baseline and after four months of exercise training or usual care.

AET Protocol: Four-month supervised exercise training was performed in the hospital three times a week, 60-min exercise sessions (48 sessions in total). Each session consisted of 40min on a treadmill, 15 min of personal light resistance training (including chest press, squat, pull down, leg extension, shoulder press, calf raises, leg curl, and sit-ups), and 5min of cool down and stretching. The AET was individually prescribed according to their heart rate (HR) from maximal cardiopulmonary exercise testing (CPT), and patients exercised between the ventilatory threshold (VT) and respiratory compensation point (RCP). HR, systolic blood pressure, oxygen saturation, and exhaustion (i.e., Borg scale from 7 to 20) were monitored during the sessions. An exercise physiologist supervised all sessions. In the first 12 weeks, HR was maintained at T frequency. Between the 12th to 24thweek, there was a progressive increase in the effort, and HR was supported between AT and RCP. In the last 12 sessions of the program, HR was maintained close to RCP frequency.

IMT Protocol: Four months of exercise training were carried out daily, three sets of 30 repetitions using the POWERbreathe® device (POWERbreathe International Limited, Southam, UK), three sets of 30 repetitions. Maximal inspiratory pressure (MIP) measures were performed in all patients before the intervention, and patients exercised at 60% of individual MIP. Patients were instructed to inhale using diaphragm musculature, trying to expand the rib cage to avoid the use of accessory muscles, and breathing at a rate of 12 to 16 breaths/min. A nose clip was worn to ensure patients breathed exclusively through the training device. All patients had a supervised session of IMT with a physiotherapist once a week for the first two months and once every two weeks for the last two months. The load was adjusted during the supervised sessions. Patients were encouraged to maintain their habitual activities during the protocol.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Sao Paulo, Brazil, 05403000
        • InCor Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Both gender, aged between 12 and 30 years
  • Patients undergoing the Fontan operation with time postoperatively ≥5 years
  • Clinically stable patients, no arrhythmia in the last electrocardiogram or clinical assessment
  • Consent by the cardiologist
  • Patients who voluntarily signed the consent form.

Exclusion Criteria:

  • Patients with hypoplastic left heart syndrome
  • Changes that reduce musculoskeletal walking skills
  • Neurological sequelae, patients with associated genetic syndrome, disturbance cognitive or psychiatric
  • Patients with a history of ventricular arrhythmias, cardio respiratory arrest, users of anti-arrhythmic drugs and / or underwent implantation of pacemaker
  • Atrial arrhythmia requiring treatment in the last 6 months
  • Patients with heart failure not controlled by medications and lung hypertension
  • Patients with protein-losing enteropathy
  • Severe hypoxemia (oxygen saturation <80% at rest)
  • Symptomatic patients with a diagnosis of diaphragmatic paresis or paralysis postoperative patients, with or without plication
  • Patients with moderate to severe asthma
  • Patients who live outside the area of Sao Paulo

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Aerobic Exercise Training Group
Aerobic Training: Aerobic training and muscle strength exercise for upper and lower limbs, 3 times a week for 4 months.
Other: Aerobic Exercise Training
Supervised aerobic and light muscle resistance exercise training
Other Names:
  • AET
Active Comparator: Inspiratory Muscle Training Group
Respiratory Training: muscle training using POWERbreathe device, 7 times a week, 3 series of 30 repetitions per day, for 4 months.
Other: Inspiratory Muscle Training
Inspiratory muscle training with POWERbreathe device
Other Names:
  • IMT
Active Comparator: No Exercise Trainint Group
No Physical Activity: Control group (usual care)
Other: No Exercise Training
Usual care
Other Names:
  • NET

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement exercise tolerance and physical capacity
Time Frame: Baseline and 4 months
Change in parameters by cardiopulmonary exercise test; increase in lung volumes and capacities; improvement by neurovascular control and skeletical muscle metabolism
Baseline and 4 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in the functional capacity post exercise training program
Time Frame: baseline and 4 months
Increase at least 20% cardiopulmonary exercise test parameters: VO2 peak, oxygen pulse and VE/VCO2 slope
baseline and 4 months
Improvement in pulmonary function post physical exercise program
Time Frame: baseline and 4 months
Achieve at least 80% of predicted values for age at pulmonary function testing: spirometry, plethysmography, carbon monoxide diffusion capacity and maximal inspiratory pressure
baseline and 4 months
Change in autonomic function post exercise training program
Time Frame: baseline and 4 months
Decrease bursts/min and bursts per 100 heart beats by at least 20% from baseline by directly measured by microneurography : direct muscle sympathetic nerve activity (MSNA)
baseline and 4 months
Improvement in peripheral blood flow post exercise training program
Time Frame: baseline and 4 months
Increase forearm blood flow in mL/min/100mL
baseline and 4 months
Change in the plasma epinephrine level post exercise training program
Time Frame: baseline and 4 months
Decrease of plasma epinephrine level from baseline
baseline and 4 months
Change in muscle metabolism post exercise training program
Time Frame: baseline and 4 months
Increase of the amplitudes of the phosphocreatine, inorganic phosphate and ATP from baseline by 31P-MRS: Quadriceps femoral 31P-MRS
baseline and 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

  • Study Chair: Marcelo B Jatene, MD,PhD, Heart Institute, University of Sao Paulo, Medical School
  • Principal Investigator: Aida LR Turquetto, PhD student, Heart Institute, University of Sao Paulo, Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2013

Primary Completion (Actual)

January 30, 2016

Study Completion (Actual)

October 30, 2020

Study Registration Dates

First Submitted

September 3, 2014

First Submitted That Met QC Criteria

October 31, 2014

First Posted (Estimate)

November 5, 2014

Study Record Updates

Last Update Posted (Estimate)

December 7, 2022

Last Update Submitted That Met QC Criteria

December 3, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAAE 01998712.7.0000.0068

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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