Effect of Fetal Aortic Valvuloplasty on Outcomes

Recruiting

• Conditions: Hypoplastic Left Heart Syndrome; Congenital Heart Disease; Aortic Valve Stenosis; Fetal Cardiac Disorder
• Interventions: Procedure: Fetal aortic balloon dilatation

• Registration Number: NCT05386173
• Lead Sponsor: Queen Silvia Children's Hospital, Gothenburg, Sweden

Brief Summary

In one of the most severe congenital heart defects, hypoplastic left heart syndrome (HLHS), the left ventricle is underdeveloped and the prognosis is worse than in most other heart defects. The underdevelopment can occur gradually during fetal growth caused by a narrowing of the aortic valve. At some international centers, such fetuses are treated with a balloon dilation of the narrowed valve, but there is no scientifically sound evidence that this treatment is effective.

The aim of this study is: 1/ to evaluate whether balloon dilation during the fetal period of a narrowed aortic valve can reduce the risk of the left ventricle becoming underdeveloped and the baby being born with a so-called univentricular heart (HLHS); 2/ to investigate whether such treatment improves the prognosis for this group of children with a very complex and severe heart defect and 3/ to also describe side effects and risks in fetuses and mothers of the fetal procedure.

Detailed Description

Routinely collected pre- and postnatal clinical data will be entered into a digital database and echocardiographic examinations will be uploaded to a server. A core lab will measure and analyze all echocardiographic examinations according to protocol. The growth of the left heart structures and the postnatal outcome will be compared between the intervention and non-intervention groups.

The decision whether a fetal balloon dilatation shall be attempted is not part of the study protocol. The number of examinations of mother/fetus/infant in this study is not different from the number of examinations that will be recommended for someone choosing not to be part of this study. Participation in the study does not affect the care and treatment mothers and fetuses are receiving during pregnancy, nor how the infant is examined and treated after birth.

Study Timeline

• Study Start: 2021-01-01
• Study First Submitted: 2022-05-13
• Study First Submitted QC: 2022-05-18
• Study First Posted: 2022-05-23
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-21
• Primary Completion: 2029-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

A. All of the following echocardiographic criteria need to be satisfied between 23+0 and 31+6 weeks (z-scores according to Schneider et al):

1. Aortic valve stenosis with antegrade flow through the valve

2. Predominantly left-to-right shunt at the atrial level

3. Predominantly retrograde flow in the aortic arch between the first two brachiocephalic vessels

4. Qualitatively depressed left ventricular function

5. Left ventricular end-diastolic diameter Z-score > ±0

6. Left ventricular inlet length in diastole :

   1. Gestational age ≤ 24+6: Z-score > ±0
   2. Gestational age 25+0 to 27+6: Z-score > -0.75
   3. Gestational age ≥ 28+0: Z-score > -1.50

7. Mitral valve diameter in diastole Z-score > -2.0

B. All of the following postnatal treatment options need to be available: 1. Surgical or catheter based aortic valvotomy 2. Ross-Konno surgery 3. Norwood or hybrid stage-one surgery

Exclusion Criteria

1. Any associated cardiac defect except persistent left superior vena cava and coarctation of the aorta
2. Any significant (i.e. that might influence outcome) extracardiac anomaly and/or known chromosomal aberration. Also, if such a condition is present at inclusion but diagnosed only after birth the case will be retrospectively excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Fetal intervention group	Fetal aortic balloon dilatation	Fetuses with aortic valve stenosis satisfying all of the inclusion/exclusion criteria

Primary Outcome Measures

Name	Time	Method
Transplantation-free survival	Follow-up from study inclusion during fetal life until 2 years postnatal age	Transplantation-free survival from fetal diagnosis to 2 years postnatal age with a biventricular circulation without pulmonary hypertension at that time. Absence of pulmonary hypertension is defined as a TR max velocity ≤ 2.8 m/s with no other echocardiographic signs of pulmonary hypertension and/or catheter data showing a mean pulmonary arterial pressure \<25 mmHg.

Secondary Outcome Measures

Name	Time	Method
Intervention-related fetal death	From the time of fetal intervention until 24 hours after the intervention	Intervention-related fetal death (defined as fetal death within 24 hours of procedure)
Maternal complications to fetal intervention procedure	From time of fetal intervention until 24 hours after the intervention	Maternal complications to procedure requiring intensive care or resulting in maternal death
Preterm delivery	From time of fetal intervention until 37 weeks gestational age, maximum 14 weeks	Preterm delivery before 37 weeks gestational age
Fetal death not directly related to the intervention	From 24 hours after fetal intervention until fetal death, up to 20 weeks after study inclusion.	Fetal death not directly related to the intervention, except termination of pregnancy
Fetal left heart growth	From the date of study inclusion until just before the first postnatal catheter or surgical intervention, or death, whichever comes first, total time frame 7 months	Fetal left heart growth as measured with dimensions expressed a z-scores of the mitral valve diameter, left ventricular inlet length and aortic valve diameter

Trial Locations

Locations (13)

Congenital Heart Collaborative, Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Department of Pediatrics, Umeå University Hospital; 🇸🇪 Umeå, Sweden

Fetal Medicine Unit, Dept. Obstetrics & Gynecology University Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Fetal Cardiovascular Program, University of California San Francisco; 🇺🇸 San Francisco, California, United States

The Hospital for Sick Children Toronto; 🇨🇦 Toronto, Canada

Pediatric Cardiology - University Hospital Bonn; 🇩🇪 Bonn, Germany

Department of Pediatric Cardiology, Skane University Hospital; 🇸🇪 Lund, Sweden

Department of Pediatric and Congenital Cardiology, University of Heidelberg; 🇩🇪 Heidelberg, Germany

Department of pediatric cardiology, Karolinska Institute; 🇸🇪 Stockholm, Sweden

University hospital Technical university, mother- and-child center; 🇩🇪 Munich, Germany

Department of Perinatal Cardiology and Congenital Anomalies, Centre of Postgraduate Medical Education.; 🇵🇱 Warsaw, Poland

Kinderherzzentrum Linz; 🇦🇹 Linz, Austria

Department of Paediatric Cardiology, Helsinki University Children's Hospital; 🇫🇮 Helsinki, Finland