With the improvement in the detection of congenital heart disease in fetal life, fetal cardiac interventions are pushing the envelope in hopes of either altering the natural history of disease or improving survival in certain high-risk lesions. These interventions include fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome, fetal atrial septoplasty with or without atrial septal stenting for hypoplastic left heart syndrome and variants with intact or severely restrictive atrial septum, and fetal pulmonary valvuloplasty for severe pulmonary stenosis or pulmonary atresia with intact ventricular septum. This review discusses their indications, technical aspects, and outcomes based on available literature.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV.

OBJECTIVE: To report our experience of fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS), with a focus on the postnatal evolution of the patients.
METHODS: This was a retrospective study including all fetuses with critical AS which underwent FAV in a single center between January 2011 and June 2022. FAV was performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the antegrade aortic flow across the aortic valve. At birth, a biventricular circulation (BVC) strategy was decided assuming the left ventricular (LV) systolic and diastolic function would ensure the systemic circulation.
RESULTS: Sixty-three FAV procedures were performed in 58 fetuses, at a median (range) gestational age of 26.2 (20.3-32.2) weeks. The procedure was technically successful in 50/58 (86.2%) fetuses. There were 11/58 (19.0%) cases of in-utero demise and 9/58 (15.5%) terminations of pregnancy. No patient was liveborn after an unsuccessful procedure. Thirty-eight (65.5%) infants were liveborn, at a median (range) gestational age of 38.1 (29.0-40.6) weeks, of whom 21 (55.3%) required prostaglandin treatment. Twenty-eight of the 38 (73.7%) liveborn children (48.3% of the study population) entered the BVC pathway at birth. Among them, 20 (71.4%) required an aortic valvuloplasty procedure at birth (11 (55.0%) percutaneous balloon, nine (45.0%) surgical) and eight (28.6%) did not require any treatment at birth, but, of these, five (62.5%) underwent surgical valvuloplasty between day 26 and day 1200 of age. Eleven (39.3%) of the infants with BVC at birth required a second intervention and four (14.3%) of them required a third intervention. Two (7.1%) infants who entered the BVC pathway at birth underwent conversion to univentricular circulation (UVC). None of the surviving children with BVC developed pulmonary hypertension. The overall survival rate in those with BVC at birth was 22/28 (78.6%) at a median (range) follow-up of 23.3 (2.0-112.6) months. Ten of the 58 (17.2%) patients had UVC at birth. Among these, six (60.0%) received compassionate care from birth and four (40.0%) underwent surgery. Three of the 10 patients who had UVC at birth were still alive at the latest follow-up assessment, at a median (range) gestational age of 24.3 (8.3-48.7) months.
CONCLUSIONS: FAV for critical AS led to increase of antegrade aortic flow in 86.2% of fetuses, with BVC being achieved in 48.3% (73.7% of the liveborn cases). Among patients with BVC at birth, the rate of reintervention was high, but 78.6% of these children were alive at the latest evaluation. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested.

Critical aortic stenosis that appears in mid-gestation tends to develop to growth retardation of left ventricle, known as hypoplastic left heart syndrome (HLHS). Despite better clinical management of HLHS, the morbidity and mortality rates of univentricular circulation patients remain high. In this paper, we sought to perform a systematic review and meta-analysis to know the outcomes of fetal aortic valvuloplasty in critical aortic stenosis patients.
This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. A systematic search on fetal aortic valvuloplasty procedure for critical aortic stenosis was performed through PubMed, Scopus, EBSCOhost, ProQuest, and Google Scholar. The primary endpoint of each group was overall mortality. We used R software (version 4.1.3) to estimate the overall proportion of each outcome using random-effects model of proportional meta-analysis.
A total of 389 fetal subjects from 10 cohort studies were included in this systematic review and meta-analysis. Fetal aortic valvuloplasty (FAV) was successfully performed in 84% of patients. It revealed a successful conversion to biventricular circulation rate of 33% with a mortality rate of 20%. Bradycardia and pleural effusion requiring treatment were two most common fetal complications, whereas maternal complication reported was only placental abruption in one patient.
FAV has a high technical success rate with the ability to achieve biventricular circulation and a low rate of procedure-related mortality if carried out by experienced operators.

Fetal aortic valvuloplasty may prevent the progression of severe fetal aortic stenosis to hypoplastic left heart syndrome at birth. Since it is an high risk procedure a careful selection of fetuses that can benefit from the prenatal treatment instead of waiting for postnatal intervention.

During fetal life some cardiac defects may lead to diminished left heart growth and to the evolution of a form of hypoplastic left heart syndrome (HLHS). In fetuses with an established HLHS, severe restriction or premature closure of the atrial septum leads to left atrial hypertension and remodeling of the pulmonary vasculature, severely worsening an already poor prognosis. Fetal therapy, including invasive fetal cardiac interventions and non-invasive maternal hyperoxygenation, have been introduced to prevent a possible progression of left heart hypoplasia, improve postnatal outcome, or secure fetal survival. The aim of this review is to cover patient selection and possible hemodynamic effects of fetal cardiac procedures and maternal hyperoxygenation in fetuses with an evolving or established hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a life-threatening congenital heart disease that is characterized by severe underdevelopment of left heart structures. Currently, there is no cure, and affected individuals require surgical palliation or cardiac transplantation to survive. Despite these resource-intensive measures, only about half of individuals reach adulthood, often with significant comorbidities such as liver disease and neurodevelopmental disorders. A major barrier in developing effective treatments is that the etiology of HLHS is largely unknown. Here, we discuss how intracardiac blood flow disturbances are an important causal factor in the pathogenesis of impaired left heart growth. Specifically, we highlight results from a recently developed mouse model in which surgically reducing blood flow through the mitral valve after cardiogenesis led to the development of HLHS. In addition, we discuss the role of interventional procedures that are based on improving blood flow through the left heart, such as fetal aortic valvuloplasty. Lastly, using the surgically-induced mouse model, we suggest investigations that can be undertaken to identify the currently unknown biological pathways in left heart growth failure and their associated therapeutic targets.

Fetal cardiac intervention is an in-utero cardiac procedure done in fetuses with heart diseases like severe aortic stenosis with evolving hypoplastic left heart syndrome, hypoplastic left heart syndrome with an intact or restricted atrial septum, pulmonary atresia with an intact ventricular septum, fetal heart block obstructed total anomalous pulmonary venous return, pericardial collection. The successful biventricular repair can be done in postnatal life after aortic or pulmonary valvuloplasty. Fetal bypass is very challenging because of different physiology. Low prime volume with the high flow can be used to prevent an inflammatory response.

OBJECTIVE: Fetal aortic valvuloplasty (FAV) became a treatment option for critical fetal aortic stenosis (AS) with the goal to preserve biventricular circulation (BVC). To date, it is unclear how many patients undergoing FAV achieve a BVC. Therefore, the goal of this systematic review/meta-analysis is to investigate the type of postnatal circulation following FAV.
METHODS: The methodology published by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was applied. A systematic search on peri- and postnatal outcome in patients with AS following FAV was performed using MEDLINE, EMBASE, Web of Science and Cochrane Library. All literature was assessed by reading abstracts, excluding duplicates, and if suitable, full text articles were obtained and included. We reviewed publications from 2000 to 2020 including at least 12 months of follow-up. Review papers, comments, books, editorials and case reports were excluded. The primary endpoint was type of postnatal circulation. Additional assessed outcomes included fetal death, live birth, neonatal death (NND), termination of pregnancy (TOP) and technical success of FAV procedure. The quality of articles was assessed using the Critical Appraisal Skills Programme tool (CASP checklist). To estimate the overall proportion of each endpoint, meta-analysis of proportions was employed using a random-effects model.
RESULTS: An electronic search identified 579 studies, of which seven were considered eligible for analysis. A total of 266 fetuses underwent FAV with a follow-up ranging from 12 months to 13.2 years. There were no maternal deaths and only one FAV related maternal complication. Hydrops was present in 25 (9%) patients. Pooled prevalence of BV and UV among all live-born patients were 46% (95% CI: 39.2, 52.4) and 44 %, (95% CI: 33.9, 53.8), respectively. Pooled prevalence of each secondary outcome was, technical successful procedures (82%; 95% CI: 74.3, 87.9), fetal deaths (16%; 95% CI: 11.2-22.4), TOP (6 %; 95% CI: 2.0-15.5), live-births (79 %; 95% CI: 66.5, 87.4), NND (9%; 95% CI 4.7, 15.5), comfort care (4%; 95% CI: 1.9, 8.4), late death (10%; 95% CI: 3.6, 26.1). Pooled prevalence for BV and UV among live-born patients that underwent technical successful procedures were 52% (95% CI: 44.7, 59.1) and 39.8 % (95% CI: 29.7, 50.9), respectively.
CONCLUSIONS: This study showed a BVC rate of 46% among live-born patients with AS undergoing FAV. Bias might be introduced due to the lack of randomized clinical trials and BVC rate improved to 52% when subjects underwent a technically successful FAV. However, currently, data does not suggest a true benefit after FAV towards BVC. This article is protected by copyright. All rights reserved.