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