Cardiac Imaging in congenital aortic stenosis: unravelling risk factors and predicting clinical outcome

Congenital aortic stenosis (ConAoS) accounts for 4-8% of all congenital cardiac
diagnoses. It is often caused by a bicuspid aortic valve (BAV), which has an
estimated prevalence of 0.5-2% in the general population. Patients with ConAoS
may remain asymptomatic, but gradual deterioration of the stenosis and the
strong association of BAV with aortic dilatation contributes to important
morbidity and mortality. The prevalent nature of this heart defect implies an
important health problem resulting in hospitalization and (re-) interventions.
As it is still largely unknown which markers predict adverse outcome, the aim
of this study is to evaluate trends in imaging and biomarkers in this patient
population and their relation with clinical outcome.

It is increasingly acknowledged that aortic stenosis is not only a disease of
the valve, but also of the left ventricle (LV) and the aorta. In the course of
disease progression, pressure overload and ventricular wall stress lead to
remodeling of the LV, which eventually leads to left ventricular hypertrophy
(LVH) and myocardial fibrosis. Although these processes have been described in
patients with aortic stenosis, little is known about the prevalence and
prognostic relevance of LVH and myocardial fibrosis in patients with ConAoS,
who are often relatively young. Applying upcoming innovative imaging modalities
such as high frame rate echocardiography and T1-mapping in patients with ConAoS
will increase our knowledge on tissue characterization, which in turn will
facilitate identifying patients at high risk for complications and rapid
disease progression.

The CAS study is a clinical observational study investigating the effects of
ConAoS on the left ventricular function and the prevalence, pattern and expanse
of LVH, myocardial stiffness and myocardial fibrosis. Moreover, we will assess
the prognostic capacity of the presence of these pathological processes,
correlating our findings at baseline to clinical outcome by assessing the
occurrence of cardiovascular events and all-cause mortality during 3-year
clinical follow-up. We will unravel biomarker and imaging predictors for
myocardial dysfunction (systolic and diastolic) with specific attention for
male-female differences.
This newly gained knowledge will enable us to improve and individualize current
treatment protocols and derive novel therapeutic strategies for adult patients
with ConAoS.

The general aim of this study is to gain knowledge on the impact of ConAoS in
adult patients, studying the aortic valve itself, the left ventricle and the
aorta.

The following primary objective is conducted: to describe the prevalence and
pattern of myocardial fibrosis in patients with ConAoS.

Prospective observational cohort study with 3-year clinical follow-up,
conducted at the Erasmus MC.

The burden of participation is limited because of the non-invasive nature of
the investigations and because the majority of the investigations are part of
routine care. Additional burden for participants is mostly attributed to the
more extensive nature of the CMR and echocardiography, leading to a greater
time investment for the participants. Generally, CMR and echocardiography
examinations are tolerated well. Adverse events are rare, but can occur due to
the use of contrast agents during the investigations. To minimize the burden
for patients, all examinations will be planned at one day.
There are no benefits for participants, besides the contribution to new
knowledge and insights on ConAoS, which will in the future hopefully lead to
better diagnostic methods and treatments.