4D flow hemodynamics in the great arteries in children and adults after arterial switch operation for transposition of the great arteries

Transposition of the great arteries (TGA) is one of the most common cyanotic
congenital heart diseases. With a prevalence of 3.45 per 10000 live births in
Europe, it is the fourth most common type of major cardiac defect, representing
5% of all congenital heart diseases. Uncorrected children with TGA have no
change to survive.
The first successful arterial switch operation (ASO) for correction TGA was
performed by Jatene in 1975. From the mid 1980s the ASO became routine and
currently the ASO is the operation of choice in the majority of patients with
TGA. The procedure involves translocation of the pulmonary artery and aorta
above the level of the sinuses and re-implantation of the coronary ostia in the
neoaorta. As a result the original pulmonary valve and proximal main pulmonary
artery become the neoaortic valve and proximal neoaorta.
Despite excellent early and long-term survival, important residual lesions are
increasingly recognized, including dilation of the neoaortic root, neoaortic
valve regurgitation, pulmonary arterial stenosis, coronary problems and
progressive left ventricular dysfunction. All these factors have been
correlated to diminished exercise capacity and reoperations and catheter-based
interventions are required 15-20% of patients after ASO during long-term
follow-up, till now.

Neoaortic dilation is present in the majority of children and adult patients
after ASO. The aortic root dilation is progressive even in adulthood up to 35
years after ASO, with potential complications as neoaortic valve regurgitation,
pulmonary artery branch stenosis and development of an acute angle of the
coronary origin, resulting in ostial stenosis, increased risk of coronary
kinking or wedging of the coronary arteries between the great vessels.
Obviously, neoaortic root pathology plays a central role in the management of
patients with TGA during follow-up after ASO and concerns are being expressed
about the increased need for aortic root reoperation in future. Besides
dilation, alterations in intrinsic vessel characteristics, e.g. reduced
elasticity and increased stiffness have been observed in this patient
population. All these changes can impair left ventricular function.

A second important factor for the preservation of adequate left ventricular
function and preservation of normal exercise capacity is an optimal coronary
circulation. In a certain percentage of the patients after ASO problems in
myocardial perfusion due to coronary problems are seen, even in asymptomatic
patients of all ages. Coronary re-implantation at a young age, progressive
aortic root dilation and aortic stiffness over time are potential risk factors
for development of myocardial tissue alterations (scarring/fibrosis) and
secondary left ventricular dysfunction.

The application of 4D flow can provide new insights in the pathogenesis of the
development of aortic root pathology in children with TGA. Furthermore, these
hemodynamic flow assessments can be used to study the interaction of the
enlarged neoaortic root and pulmonary flow patterns as branch pulmonary artery
stenosis is a common problem which often requires reoperation and
catheter-based interventions after ASO for TGA. In particular, 4D flow in
combination with dobutamine induced stress imaging to evaluate the dynamic
effect of the expansion of the neoaortic root with increasing stroke volumes on
pulmonary artery dimensions and pulmonary flow patterns. Also of special
interest are the effects of dobutamine stress on aortic flow profiles, aortic
wall shear stress and wall distensibility in relation to the systolic and
diastolic cardiac function (e.g. ventriculo-arterial interaction).

The etiology neoaortic root pathology is not clear and research on these
pathophyological mechanisms leading to neoaortic root dilatation (with 4D MRI)
and the evaluation of myocardial function and early myocardial tissue
alterations are essential for these patients to prevent them from
cardiovascular problems in future.

1. The application of 4D flow MR imaging to analyse blood flow patterns (flow
angle, flow asymmetry), regional vessel wall parameters (regional wall shear
stress, vessel wall thickness) and pulsed-wave velocity in neoaortic root,
carotid artery and distal aorta in TGA patients after ASO and age-matched
controls.
2. To study the static and dynamic influence of aortic root dilation in rest
and especially with dobutamine stress on neopulmonary blood flow profiles using
4D flow MR imaging.
3. To study the role of aortic flow hemodynamics in relation to aortic root
dilation and geometry in patients after ASO for TGA based on conventional MRI
and 4D flow MR imaging.
4. To evaluate and compare the ascending aorta flow hemodynamics in TGA
patients after ASO with tricuspid and bicuspid neoaortic valves using 4D flow
MR imaging.
5. To evaluate cardiac reserve, left ventricular function and left ventricular
myocardial alterations with dobutamine stress CMR in comparison to exercise
capacity levels and impedance cardiography parameters.

Cross-sectional cohort study. Inclusion of 67 patients after arterial switch
operation for transposition of the great arteries (TGA) and 60 healthy
volunteers of same age. From the 67 TGA patients, 60 patients will have a
tricuspid neo-aortic valve, 7 patients will have bicuspid neo-aortic valve (no
more patients with bicuspid neo-aortic valve available in the CAHAL cohort).
All patients underwent an cardiac MRI (including dobutamin stress imaging),
echocardiography, ambulatory 24-hour holter (including impedance cardiography)
and an exercise capacity test with investigation of oxygen uptake and work
load. Healthy volunteers (over 12 years of age) will underwent same MRI
protocol with exclusion of dobutamin stress imaging. No exercise capacity
testing and 24-hour holter will be done in the healthy volunteers due to the
existence of good reference values.

All clinical examinations are the same as are routinely performed during
follow-up of patients operated for transposition of the great arteries, except
for dobutamine stress and 4D flow imaging during MR examination, resulting in
extra scanning time: two times 15 minutes. For the nature and extent of the
burden and risks associated with these investigations I would like to refer you
to the answers on the question of items E2, E9, E9a and E10 of this document.