High intensity interval training in patients with a right ventricle to pulmonary artery conduit

Congenital heart disease (CHD) is the most common birth defect and represents a
collection of relatively common and rare disorders characterized
by abnormal anatomy of the heart. One group of patients suffers from imperfect
connection of the right ventricle to the pulmonary artery, limiting blood
supply to the lungs. CHD in this group of rare disorders includes truncus
arteriosus, pulmonary atresia and tetralogy of Fallot with severe right
ventricular outflow obstruction. To ensure blood flow to the pulmonary
vasculature, a surgically implanted connection of the right ventricle to the
pulmonary arteries, a right ventricle to pulmonary artery (RV-PA) conduit, is
required.
In general, survival of patients with CHD, including the mentioned types, has
increased over the past decades, leading to an increased prevalence of
long-term sequelae. Heart failure is one of the critical long-term sequelae of
CHD, affecting life expectancy and quality of life, with a current lack of
effective therapy. Especially patients with diseases of the right ventricle, as
in the mentioned group, have a serious risk of heart failure at a young age,
with over 45% having heart failure at an average age of 30 years.
Hence, there is a need for preventive strategies. Exercise training may be such
a preventive strategy. In patients with cardiovascular disease in general, a
higher exercise capacity reduces the risk for adverse events. In patients with
CHD, several studies suggest that specific types of exercise training may
improve exercise capacity. Unfortunately, patients with rare forms of CHD, e.g.
patients with truncus arteriosus are understudied. It is unknown whether
results obtained from other disease groups are applicable to this type of CHD.
Also, patients with other rare forms of CHD characterized by an RV-PA conduit
are less well studied. The presence of such a conduit increases the risk of
residual lesions, which may have reduced inclusion in previous studies.
We hypothesize that an exercise training program in patients with an RV-PA
conduit will elicit similar responses in exercise capacity as has been
demonstrated by previous studies in patients with other types of CHD. We will
test this hypothesis in the proposed intervention study. With growing evidence
for similar or superior results of high-intensity interval training (HIIT)
compared to aerobic training in a more time-efficient fashion, we will use a
HIIT program.
Yet, previous studies testing the response to exercise training in patients
with CHD yielded an average increase, albeit the groups are composed of
responders and non-responders. The profile of (non-)responders has not been
identified yet. If there is a biomarker predicting response to therapy, this
may be useful to select patients for exercise therapy, which requires a large
amount of patient commitment. Therefore, our secondary aim is to identify
predictors for response to exercise training.

Primary Objective:
To assess the efficacy, expressed by change in peak oxygen consumption obtained
with cardiopulmonary exercise testing (CPET), of a HIIT program in patients
with an RV-PA conduit.

Secondary Objective(s):
To determine predictors for response to exercise training, obtained using CPET,
echocardiography, magnetic resonance imaging (MRI), gut microbiome analysis and
blood biomarker profile.

The study is a randomized controlled trial with a modified cross-over design.
Participants will be randomized into two groups, one intervention and one
control group. The intervention and control period will last 12 weeks, in which
the intervention group will receive a standardized HIIT program, and the
control group will continue exercise as usual. Before and after this time
period there will be a study visit with measurements, including CPET,
echocardiography, MRI, gut microbiome analysis, collection of blood and
questionnaires on quality of life and daily physical activity level. After 12
weeks, the control group will receive the same intervention as participants
from the intervention group, with a third study visit after this period. At the
regular outpatient clinic visit one year after completion of the study,
participants will be provided questionnaires of quality of life and daily
physical activity.

12-week high intensity interval training program, semi-supervised (online),
three times a week.

The burden associated with participation mainly consists of a time investment.
Participants will exercise three times a week and will attend two or three
study visits at the hospital. The amount of time spent for exercise training is
also part of the general recommendations of the World Health Organization.
Procedures performed during study visits are part of standard follow-up in
these patients (except for gut microbiome analysis), with one or two additional
visits due to participation in the study.
Included participants will have no restrictions in their level of physical
exercise. In daily life, they can be subject to peak physical exercise levels.
In our previous experience no untoward effects have been observed in exercise
testing or training. Heart rhythm disturbances may occur during CPET. CPET is
performed with close monitoring of vital parameters and under supervision of a
medical doctor. No (serious) adverse events have been reported with exercise
training in patients with CHD.
Participants may benefit from the proposed positive effects of exercise
training, based on the current literature. We will include patients with an
RV-PA conduit, because this is an understudied population in which long-term
complications such as heart failure are a major issue. The study population
will include children and young adults, in order to obtain a group that has
been treated according to current surgical strategies and to be able to study
exercise training as a preventive strategy, so before overt heart failure is
present.