Fetal development of the left ventricular myocardium in left sided congenital heart defects

Aortic coarctation (CoA) is a life-threatening cardiac defect which frequently
requires surgery in the first year of life. CoA comprises 5-8% of all
congenital heart defects. Prenatal diagnosis is critically important, as timely
management with prostaglandins after birth reduces neonatal morbidity and
mortality in severe cases. Prenatal identification of CoA is, however,
challenging. Ventricular and semilunar valve size disproportion with a smaller
left side on fetal ultrasound are known predictors of CoA, but sensitivity is
moderate and specificity is low. The high false-positive rate can be attributed
to the fact that distinction between a pathological ventricular size
disproportion and normal physiological right-sided dominance is difficult,
especially late in gestation. False-positive diagnosis may result in parental
anxiety and unnecessary neonatal intensive care admissions immediately after
birth.

Prenatal detection of more severe cases (significant ventricular disproportion
or aortic arch hypoplasia) is easier since these fetuses have dramatically
altered ultrasonographic findings. In these cases, however, it is difficult to
predict the left ventricular development in time. Parents and health care
providers are faced with the uncertainty whether the left ventricle of the
fetus will reach a sufficient size to support the systemic circulation after
birth. Some cases may develop hypoplastic left heart syndrome (HLHS), a
condition with high morbidity and severity.

Over the past decade, most studies have focused on the improvement of prenatal
detection of CoA. However, the underlying pathophysiology why cases with
similar ultrasonographic appearance develop differently is still not fully
understood. Differences in fetal myocardial development and morphology, leading
to differences in myocardial function and deformation, could play a role.
Tools to assess fetal myocardial development comprise new ultrasonographic
techniques like color Tissue Doppler Imaging (cTDI) and speckle-tracking.

We hypothesize that the left ventricle shows a different myocardial development
and function with as a result an altered blood flow pattern in fetuses with a
CoA, compared to fetuses that turn out not to have CoA postnatally. This
knowledge could contribute to a better prediction, necessary for proper
counselling.

The primary aim is to assess myocardial development and function of the left
ventricle in fetuses with the suspicion of aortic coarctation on fetal
echocardiography.

The secondary aim is to study left ventricular blood flow movement with vector
analysis in these cases.

We will conduct a single-center, non-randomized, prospective, observational
case-control study. All pregnant women with the antenatal suspicion of aortic
coarctation on fetal echocardiography will be selected. Subjects will be
followed during pregnancy and allocated to either cases or controls after
birth, according to the postnatal diagnosis and need for intervention:
- Cases: fetuses with postnatally confirmed CoA in need of an aortic arch
repair.
- Controls: fetuses with a physiological right-sided dominance of the fetal
heart: no need of a coarctation repair operation after birth.
Cases and controls will be matched for gestational age. All fetal ultrasound
examinations are conducted by experienced ultrasonographers (A.K.K. Teunissen,
physician-ultrasonographer, and F.Zwanenburg, primary investigator) at the
Leiden University Medical Center (LUMC), under supervision of M.C. Haak,
consultant in fetal medicine.

Ultrasound is a safe and non-invasive technique, which means that both mother
and fetus are not exposed to additional risks in pregnancy or after birth.
Since the only difference by participating in this study will be the additional
cardiac measurements performed during routine echocardiographic examinations,
the burden to participate is considered negligible. Participants do not have
benefits of the study.