Prognostic Model of Postnatal Circulation in Pulmonary Atresia-critical Stenosis With Intact Ventricular Septum

Development and Validation of a Prognostic Model of Postnatal Circulation in Fetuses With a Diagnosis of Pulmonary Atresia-critical Stenosis With Intact Ventricular Septum A Prospective Observational Cohort Study

Pulmonary atresia (PA)/critical stenosis (CS) with intact ventricular septum (PA/CS-IVS) is a rare congenital heart disease (CHD), that presents heterogeneously. Prognosis is conditioned by the possibility of achieving a primary repair with biventricular circulation (BV) or a one-and-a-half ventricle solution vs. a palliative approach bound to a univentricular (UV) circulation in which both survival and quality of life are significantly impaired. Predicting UV circulation prenatally is still a challenge.

The aim of this study is: 1/ to evaluate the natural history of the disease and develop a prognostic model for the prediction of transplantation-free survival with a biventricular or a one-and-a-half repair at 2 years postnatal age 2/ To develop a model to predict the risk of right ventricle dependent coronary circulation 3/ To evaluate prenatal and postnatal outcomes in non-intervened fetuses with a confirmed postnatal diagnosis of PA-CS/IVS including Intrauterine death, neonatal/Infant death, number of required postnatal procedures, need for oxygen support, need for cardiac transplantation

This is an international retrospective and prospective observational cohort study including non-intervened fetuses with a diagnosis of PA-CS/IVS between 16+0 and 28+6 weeks of gestation.

A baseline fetal ultrasound examination will be recorded for all included cases. The primary aim of the study is to develop a prognostic and validate model for the type of postnatal circulation (transplantation-free survival with a biventricular or a one-and-a-half repair at 2 years postnatal age vs univentricular palliation or transplanted).

In order to maximize the number of included cases in this rare entity, the model will be developed on retrospective data from 2013 until 2023 and validated in a prospective cohort. Cases will be recruited in referral centers regardless of their offering of fetal pulmonary valvuloplasty. However, only non-prenatally-intervened cases will be used for analysis. Fetal and postnatal echocardiographic examinations will be reviewed by a core laboratory to confirm eligibility for inclusion and identify potential measurement errors.

Data from at least one fetal echo (the first diagnostic evaluation at the referral center) and one postnatal (the first one performed after birth) will be collected, each containing a comprehensive set of two-dimensional and Doppler measurements. Additionally, one additional follow-up scan performed at least 8 weeks apart from the baseline diagnostic scan (ideally between 28 and 32 weeks) will be included in the study as well. Analysis of the prenatal change of dimensions of the right heart structures and selected hemodynamic parameters will enable comparisons between centers regardless of off-protocol center-specific postnatal treatment policies.

Inclusion Criteria:

• Absence of flow at the pulmonary valve (PA) or presence of thickened and domed. pulmonary valve cusps with a pinhole jet of flow.
• Doppler evidence of ductal-dependent pulmonary circulation.
• Intact ventricular septum.

Exclusion Criteria:

• Poor imaging windows and incomplete/poor quality scan
• Termination of pregnancy
• Cases initially included that undergo prenatal pulmonary valvuloplasty later on in pregnancy.
• Unconfirmed PA-CS/IVS at birth.
• Functional PA-CS/IVS (Ebstein malformation, monochorionic twins)
• Any associated cardiac defect except persistent left superior vena cava and aberrant right subclavian artery.
• Any significant (i.e that might influence outcome) extracardiac anomaly and/or known genetic syndromes. Also, if such a condition is present at inclusion but diagnosed only after birth, the case will be retrospectively excluded.