Effects of High-intensity Interval Training on Exercise Capacity in Patients With Grown-up Congenital Heart Disease

Congenital Heart Defects Clinical Trial

— HIIT-GUCH  

Official title:

Effects of High-intensity Interval Training on Exercise Capacity in Patients With Grown-up Congenital Heart Disease (GUCH)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02632253
• Other study ID #: HIIT-GUCH
• Status: Terminated
• Phase: N/A
• Start date: January 2016
• Est. completion date: October 2019

Study information

• Verified date: December 2020
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with congenital heart disease have long been discouraged from participating in physical exercise which has led to impaired exercise capacity in this population. Since low physical and cardiorespiratory fitness has been shown to be a predictor for hospitalization and mortality in grown-up patients with congenital heart disease (GUCH), aerobic endurance training has been recommended recently to improve exercise capacity. The aim of this study is to compare two types of training, namely high-intensity interval training (HIIT) and moderate-intensity continuous exercise (MICE), with regard to improving exercise capacity without adverse effects on heart structure, function and rhythm in the setting of a 12-week outpatient cardiac rehabilitation (CR) program in GUCH with a remaining pathology involving the right and/or left ventricles. Primary endpoint will be change in exercise capacity (maximal oxygen consumption) over the 12-week CR. Secondary endpoints will be changes of the right or left ventricles as well as vascular function. Patients with GUCH and reduced function of the right ventricle will be recruited and informed about the study within the first two weeks of CR. At the end of week 3 of the CR with supervised MICE, randomization to 9 weeks of twice weekly either HIIT or MICE takes place. MICE training is performed at an intensity of 70-85% of maximum heart rate (HRmax) for 38 min. HIIT consists of four 4 min bouts of high-intensity exercise (90-95% of HRmax), interspersed by 3 min low-intensity intervals (50-60% of HRmax). All patients complete one additional endurance activity per week in their own time with a duration of 30-60 min at moderate intensity monitored by their smart phone. Change in peak oxygen uptake as well as maximal exercise capacity at the end of an incremental cardiopulmonary exercise test will be assessed between week 3 and 12. Vascular function will be assessed at the same time. Volumes and function of the right and left ventricles will be measured by cardiac magnetic resonance imaging (CMR) upon inclusion into the study and at completion of the intervention. Furthermore, laboratory markers for heart failure as well as occurrence of irregular fast heart beats will be assessed.

Description:

Background Adults with congenital heart disease have long been recommended to refrain from physical exercise. Therefore, they often have significant reduction in exercise capacity. Only recently, regular exercise has been shown to be safe and is nowadays recommended for patients with congenital heart disease. As a result, exercise based rehabilitation programs have been implemented in order to improve exercise capacity and avoid adverse effects associated with inactive lifestyle. Several studies have shown that high-intensity interval training (HIIT) is more effective than moderate-intensity continuous exercise training (MICE) at improving functional capacity and quality of life in stable cardiac patients and can be performed safely. It has therefore emerged as a new and important exercise modality in cardiac rehabilitation centers all over Europe for stable cardiac patients with left ventricular (LV) dysfunction. However, its safety and efficacy has not yet been tested in adults with congenital heart disease and to date there are no studies who have evaluated whether short term peaks of pulmonary artery or systemic pressure during bouts of 4 min of high-intensity exercise negatively affects the subpulmonary or systemic ventricle in GUCH patients. The investigators hypothesized that the positive effects of HIIT on exercise capacity and vascular function found in patients with ischemic cardiomyopathy can be transferred to the population of GUCH patients, and that short-term bouts of high-intensity exercise will not negatively affect cardiac morphology and function. Objective To test the superiority of a 9-week high-intensity interval training (HIIT) over a standard rehabilitation training based on moderate-intensity continuous exercise (MICE) on exercise capacity in patients with grown-up congenital heart disease (GUCH) with a residual pathology involving the right and/or left ventricle (RV/LV). Methods Measurements will be performed before and after a 12 week intervention with either HIIT or MICE training. Patients will undergo cardiopulmonary exercise testing on a cycle ergometer to determine exercise capacity and VO2 peak. Cardiac magnetic resonance imaging will be performed for ventricular volumes, mass and function. Vascular function will be assessed by arterial stiffness measurement. Physical exercise, quality of life will be evaluated by questionnaires. During the 4th and the 12th week of the rehabilitation training, heart rate variability will be measured in the morning following a training, and blood samples will be taken after a training session to analyse markers of myocardial stress (hs Troponin and N-terminal of the prohormone brain natriuretic peptide, NT pro-BNP). Compliance and acceptance of training will be assessed by questionnaires.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Tetralogy of Fallot
• Double outlet right ventricle
• Transposition of the great arteries with atrial or arterial switch
• Treated or untreated pulmonary valvular or pulmonary artery stenosis
• Reduced right ventricular function after correction of atrial septal defect (ASD), atrio-ventricular septal defect (AVSD) or ventricular septal defect (VSD) (=40%)
• Ebstein anomaly
• Patients with a systemic right ventricle like d-transposition of the great arteries (d-TGA) with previous atrial switch operation or cc-TGA Exclusion Criteria
• Inability to participate in a 3-month training program in Bern
• New York Heart Association class = III
• Ventricular function =30% of either the systemic or the sub-pulmonary ventricle
• Moderate to severe LV outflow tract obstruction (valvular, subvalvular, due to asymmetric septum hypertrophy, or aortic coarctation) with mean gradient >30 mmHg by echo
• Severe RV outflow tract obstruction with peak gradient =60 mmHg by echo
• Moderate to severe pulmonary hypertension with mean pulmonary artery pressure=40 mmHg
• Resting saturation at ambient air of <90%
• Pacemaker or Implantable Cardioverter Defibrillator
• Contraindication to perform a CMR (cerebral clips, iron-containing body implants, medical pumps)
• Recent episode of ventricular tachycardia
• Permanent atrial fibrillation
• Unstable angina or recent myocardial infarction (<12 months)
• Recent cardiac operation <6 months
• Ascending aortic dilatation >45 mm in patients with bicuspid aortic valve or >50 mm in patients without bicuspid aortic valve
• Repaired coarctation with pseudoaneurysm in MR angiography
• No consent
• Any medical condition which would prevent a patient from performing high intensity training (e.g. cardiac thrombus formation, recent valve surgery (< 1 year), in general orthopedic, peripheral vascular, neurologic or other limitations)
• Inability to perform cardiopulmonary exercise testing
• Pregnancy

Related Conditions & MeSH terms

• Congenital Heart Defects
• Heart Defects, Congenital
• Heart Diseases

Intervention

Procedure:
• HIIT
High-intensity interval training (HIIT) is performed on a cycle ergometer. It consists of a 10 min warm-up followed by 4 min intervals in Zone III (at 90-95% of peak heart rate), with each interval separated by 3 min of active pauses in zone I (at 50-70% of peak heart rate). The total duration of the HIIT training is 38 min. The HIIT group will perform two supervised HIIT trainings and one self monitored MICE training per week.

Other:
• MICE
MICE is also performed on a cycle ergometer at an intensity of 70-75% of peak heart rate for 47 min (in order for the two training protocols to be isocaloric). The control group will perform two supervised and one self monitored MICE training per week.

Locations

Country	Name	City	State
Switzerland	Department of Preventive Cardiology, Bern University Hospital	Bern

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Schweizerische Herzstiftung

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Heart rate variability	Heart rate variability will be measured overnight and in the morning after a day with a training session and after a day without training.	week 3 and 12
Primary	Peak oxygen uptake (VO2 peak) during maximal cardiopulmonary exercise test	Change in VO2 peak between week 1 and 12 is measured by cardiopulmonary exercise testing on a cycling ergometer.	week 1 to 12
Secondary	VO2 peak during maximal cardiopulmonary exercise test	Change in VO2 peak between week 1 and 65 is measured by cardiopulmonary exercise testing on a cycling ergometer.	week 1 to 65
Secondary	Ventricular Volumes by cardiac magnetic resonance imaging	Left and right ventricular volumes will be assessed by cardiac magnetic resonance imaging.	week 1 and 12
Secondary	Ventricular function by cardiac magnetic resonance imaging (MR)	Left and right ventricular function will be assessed by cardiac magnetic resonance imaging (MR).	week 1 and 12
Secondary	Vascular function by arterial stiffness measurement	Vascular function will be assessed by arterial stiffness measurement.	week 3, 12, and 65
Secondary	Arrhythmias quantified and characterised by ECG	Arrhythmias will be assessed by 24-hour Holter ECG.	week 3, 12, and 65
Secondary	N terminal pro b-type natriuretic peptide (NT- proBNP)	Blood samples are taken after an exercise training session.	week 0, 3, 12, and 65
Secondary	hs Troponin	Blood samples are taken after an exercise training session.	week 3 and 12
Secondary	Adherence to training	Training session adherence will be monitored and reported as percent of prescribed training volume.	week 1-12
Secondary	Quality of life	Short form quality of life questionnaire (SF12)	week 1, 12, and 65
Secondary	Quality of life for heart failure	Minnesota quality of life questionnaire	week 1, 12, and 65
Secondary	Daily physical activity	International physical activity questionnaire	week 1, 12, and 65
Secondary	Heart rate variability	Heart rate variability will be assessed during an orthostatic challenge test.	week 3, 12, and 65