Current Understanding of Indications, Technical Aspects and Outcomes of Fetal Cardiac Interventions.

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.

Transforming congenital heart disease management: Advances in fetal cardiac interventions.

This review addresses the transformative advancements in fetal cardiac interventions (FCI) for congenital heart diseases (CHD), with a particular focus on aortic stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum, and HLHS with an intact atrial septum (HLHS-IAS). We outline the specific FCI techniques employed, the refined criteria for selecting appropriate fetal and maternal candidates, and the promising yet varied outcomes associated with these procedures. Procedural strategies and clinical decision-making are examined as we take into account the fetal pathophysiology and the benefits and risks of early intervention. We highlight the role of multidisciplinary teams in improving technical success and managing immediate procedural complications, which have led to significant improvements in procedural outcomes. Additionally, the review discusses the long-term outcomes, challenges, and future research directions in FCI, emphasizing the necessity for continuous innovation and collaboration across specialties to advance the management of CHD. The integration of new technologies and research findings holds the promise of further enhancing FCI success rates and patient outcomes.

Predicting High-Risk Fetal Cardiac Disease Anticipated to Need Immediate Postnatal Stabilization and Intervention with Planned Pediatric Cardiac Operating Room Delivery.

BACKGROUND: Distances between delivery and cardiac services can make the care of fetuses with cardiac disease at risk of acute cardiorespiratory instability at birth a challenge. In 2013 we implemented a fetal echocardiography-based algorithm targeting fetuses considered high risk for acute cardiorespiratory instability at ≤2 hours of birth for delivery in our pediatric cardiac operating room of our children's hospital, and, herein, examine our experience. METHODS AND RESULTS: We reviewed maternal and postnatal medical records of all fetuses with cardiac disease encountered January 2013 to March 2022 considered high risk for acute cardiorespiratory instability. Secondary analysis was performed including all fetuses with diagnoses of d-transposition of the great arteries/intact ventricular septum (d-TGA/IVS) and hypoplastic left heart syndrome (HLHS) encountered over the study period. Forty fetuses were considered high risk for acute cardiorespiratory instability: 15 with d-TGA/IVS and 7 with HLHS with restrictive atrial septum, 4 with absent pulmonary valve syndrome, 3 with obstructed anomalous pulmonary veins, 2 with severe Ebstein anomaly, 2 with thoracic/intracardiac tumors, and 7 others. Pediatric cardiac operating room delivery occurred for 33 but not for 7 (5 with d-TGA/IVS, 2 with HLHS with restrictive atrial septum). For high-risk cases, fetal echocardiography had a positive predictive value of 50% for intervention/extracorporeal membrane oxygenation/death at ≤2 hours and 70% at ≤24 hours. Of "low-risk" cases, 6/46 with d-TGA/IVS and 0/45 with HLHS required intervention at ≤2 hours. Fetal echocardiography for predicting intervention/extracorporeal membrane oxygenation/death at ≤2 hours had a sensitivity of 67%, specificity 93%, and positive and negative predictive values of 80% and 87%, respectively, for d-TGA/IVS, and 100%, 95%, 71%, and 100% for HLHS, respectively. CONCLUSIONS: Fetal echocardiography can predict the need for urgent intervention in a majority with d-TGA/IVS and HLHS and in half of the entire spectrum of high-risk cardiac disease.

Fetal cardiac interventions: First-year experience of a tertiary referral center in Turkey.

AIM: To present the first-year experience of fetal cardiac interventions (FCIs) in a tertiary referral hospital and to evaluate the outcomes. METHODS: This retrospective study consisted of four pregnant women who underwent fetal pulmonary or aortic balloon valvuloplasty between November 2020 and June 2021. The procedures were performed with a percutaneous cardiac puncture under the ultrasonography guidance. Gestational age at intervention, procedural success, complications, and perinatal outcomes were evaluated. Procedural complications defined as fetal bradyarrhythmia requiring treatment, pericardial effusion requiring drainage, balloon rupture, and fetal death. The procedure was considered technically successful if the valve was dilated with a balloon catheter. Ultimately successful procedure was defined as the discharge of infants alive with biventricular circulation. RESULTS: A total of 5 FCIs attempted between 26 + 3 and 28 + 2 gestational weeks. While the procedure was technically successful in 2 cases with pulmonary stenosis, both attempts were unsuccessful in the fetus with pulmonary atresia. Although the procedure was technically successful in the patient with critical aortic stenosis, it ultimately failed. No fetal death occurred in our series and there were no procedure-related significant maternal complications. However, three interventions were complicated by fetal bradycardia and pericardial effusion necessitating treatment, and balloon rupture cropped up in one case. CONCLUSION: FCIs may lead to improving the likelihood of a biventricular outcome for selected fetuses. Careful selection of patients and centralization of experience are essential for obtaining favorable outcomes. Operators should be aware of procedural complications. Improved procedural techniques with a lower complication rate will be achieved through advanced medical technology and special balloon catheters.

Speckle Tracking Analysis in Fetuses with D-Transposition: Predicting the Need for Urgent Neonatal Balloon Atrial Septostomy.

INTRODUCTION: Speckle tracking analysis of the endocardium of the right (RV) and left (LV) ventricles was used to evaluate the size, shape, and contractility of these chambers in fetuses with D-Transposition of the great arteries (D-TGA) to identify fetuses that would require emergent balloon atrial septostomy (BAS) after birth. METHODS: This was a retrospective analysis of fetuses with D-TGA and intact ventricular septum that were divided into 2 groups. Group 1 underwent urgent BAS after birth because of a restrictive atrial septum and group 2 did not. Using speckle tracking analysis, the end-diastolic and end-systolic RV and LV areas, lengths, widths, sphericity indices, and contractility were computed. Logistic regression analysis was performed to identify fetuses who would require urgent neonatal BAS. RESULTS: Of the 39 fetuses with D-TGA, 55% (n = 22) required urgent neonatal BAS (group 1) and 45% (n = 17) (group 2) did not. When comparing D-TGA groups 1 and 2, differences were seen in RV and LV area, sphericity index for segment 1 of the LV, LV fractional area of change and free wall annular plane systolic excursion, fractional shortening for LV segment 12, and RV free wall strain. Regression analysis of these measurements identified 91% of neonates who underwent BAS, with a false-positive rate of 12%. CONCLUSION: Using speckle tracking analysis to evaluate the RV and LV, measurable differences were identified for the RV and LV size, shape, and contractility between fetuses who underwent neonatal urgent BAS vs. those who did not require this procedure.

Left heart hypoplasia in the fetus: Echocardiographic predictors of outcome.

INTRODUCTION: Fetal left heart hypoplasia (LHH) with an apex-forming left ventricle may require neonatal intervention but it is difficult to predict. METHODS: We performed a retrospective study of fetuses with LHH defined as normal segmental anatomy, apex-/near-apex forming left ventricle, and ≥1 left-sided z-score ≤ -2 between 1997 and 2014. Fetuses with mitral or aortic atresia, critical aortic stenosis, extracardiac anomalies, or fetal intervention were excluded. Classification and regression tree analyses (CART) were performed to construct algorithms to predict postnatal circulation: no surgery versus biventricular surgery versus single ventricle (SV) palliation. RESULTS: Among 138 included fetuses, 52 (37%) underwent neonatal surgery, with 10 (7%) undergoing SV palliation. The strongest single outcome discriminator was exclusively left-to-right flow foramen ovale (FO) flow ≥32 weeks gestational age (GA) (seen in 0% with no surgery, 22% with biventricular surgery, 88% with SV palliation). On CART analysis >32 weeks GA, fetuses with right-to-left FO flow and aortopulmonary ratio >0.76 had 0% probability of neonatal surgery, while those with left-to-right FO flow and mitral valve z-score < -3.6 had a 70% probability of SV palliation. CONCLUSION: SV palliation is an uncommon outcome of fetal LHH. Fetal FO flow and other echocardiographic measures can help determine risk and type of postnatal intervention.

3D/4D spatiotemporal image correlation (STIC) fetal echocardiography provides incremental benefit over 2D fetal echocardiography in predicting postnatal surgical approach in double-outlet right ventricle.

OBJECTIVE: To analyze the incremental benefit of 3D/4D spatiotemporal image correlation (STIC) fetal echocardiography over 2D fetal echocardiography with respect to the accuracy of identification of anatomic details crucial for surgical decision-making and in predicting surgical approach in fetuses with double-outlet right ventricle (DORV). METHODS: This was a retrospective study of fetuses with DORV which had undergone both 2D echocardiography and 3D/4D STIC echocardiography and which underwent surgery postnatally in a tertiary pediatric cardiac center in Kerala between October 2015 and March 2019. All such cases with normal atrial arrangement, concordant atrioventricular connections and balanced ventricles were included. 2D and 3D/4D STIC fetal echocardiographic data were analyzed by two experienced observers blinded to the other dataset. Anatomic variables crucial for surgical decision-making, i.e. location and routability of the ventricular septal defect, relationship of the great arteries and presence of outflow obstruction, were compared between the two modalities with respect to agreement with postnatal echocardiography. The accuracy of prenatal prediction of the surgical pathway was compared between 2D and 3D/4D modalities with respect to the procedure undertaken. RESULTS: Included in the study were 22 fetuses with DORV which had undergone both 2D and 3D/4D imaging as well as postnatal surgery. Accuracy of prenatal interpretation of all four anatomic variables was significantly higher using 3D/4D STIC than using 2D fetal echocardiography (19/22 (86.4%) vs 8/22 (36.4%), P < 0.001). Surgical procedures included single-stage repair in 14 (63.5%) patients and a multistage approach in eight (36.4%). Prenatal prediction of the surgical pathway was significantly more accurate on 3D/4D STIC than on 2D echocardiography (20/22 (90.9%) vs 12/22 (54.5%), P = 0.021). Prenatal predictive accuracy of single-stage biventricular repair was significantly better for 3D/4D STIC than for 2D echocardiography (14/14 (100%) vs 8/14 (57.1%), P = 0.04). CONCLUSION: Addition of 3D/4D STIC to conventional 2D fetal echocardiography confers incremental benefit on the accuracy of identification of anatomic details crucial for surgical decision-making and the prediction of postnatal surgical approach in fetuses with DORV, thereby potentially aiding prenatal counseling. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[Fetal cardiac intervention and perioperative management of fetus with hypoplastic right heart syndrome].

Objective: To summarize the experience of perioperative management strategy of fetal pulmonary valvuloplasty (FPV) for hypoplastic right heart syndrome (HRHS). Methods: In the retrospective study of perioperative data, 13 fetuses of HRHS were treated with FPV in Qingdao Women and Children's Hospital from July 2018 to June 2019. Results: (1) The evaluation indexes of the right ventricle in 13 fetuses before FPV: the mean ratio of tricuspid/mitral annulus, right/left ventricular length, pulmonary/aortic annulus, and tricuspid inflow time/cardiac cycle were 0.81±0.04, 0.56±0.14, 0.69±0.06, and 0.35±0.03, respectively. (2) All pregnant mothers underwent general anesthesia. The basic fetal heart rate was (156±12) beats per minutes before FPV, and 9 fetuses showed bradycardia during the operation, and recovered to normal after drug resuscitation. On the first day after FPV, two cases had bradycardia and pregnancy was terminated. The fluctuation of systolic blood pressure of pregnant mother was less than 20%, and there was no significant difference between preoperative and intraoperative pulse pressure [(36.0±5.6) vs (35.8±6.9) mmHg (1 mmHg=0.133 kPa); t=8.102, P=0.951]. (3) All cases of HRHS fetus successfully underwent FPV. The average gestational age was (27.3±0.8) weeks. The average operation time was (23.2±1.0) minutes. The ratio of tricuspid to mitral annulus (t=-2.513, P=0.022) and the ratio of right to left ventricular length (t=-3.373, P=0.003) were significantly improved at 6 weeks postoperatively. Ten fetuses were delivered, and there was no death after early intervention. (4) Of 13 pregnant women, 3 cases were nausea and vomiting on the day of FPV operation, the treatment of the symptoms was improved by tropisetron; one case had tolerable abdominal pain and improved without special treatment. Pregnant women had no major complications such as cardiac failure, abortion and death. (5) Chromosome karyotype analysis and microarray analysis of amniotic fluid was retained during the operation. No typical chromosome abnormality or other abnormal genetic diagnosis was found. Conclusions: FPV colud be used as an effective intervention measure to promote the development of right ventricle in HRHS fetuses. The scientific management of multidisciplinary professional technical team in perioperative period is particularly important to ensure the success of FPV and the safety of pregnant women and fetuses.

An Overview of Contemporary Outcomes in Fetal Cardiac Intervention: A Case for High-Volume Superspecialization?

Fetal cardiac interventions (FCI) offer the opportunity to rescue a fetus at risk of intrauterine death, or more ambitiously to alter disease progression. Most of these fetuses require multiple additional postnatal procedures, and it is difficult to disentangle the effect of the fetal procedure from that of the postnatal management sequence. The true clinical impact of FCI may only be discernible in large-volume institutions that can commit to a standardized postnatal approach and have sufficient case volume to overcome their FCI learning curve.

Fetal cardiac interventions: Where do we stand?

Fetal cardiac intervention (FCI) is a novel and evolving technique that allows for in utero treatment of a subset of congenital heart disease. This review describes the rationale, selection criteria, technical features, and current outcomes for the three most commonly performed FCI: fetal aortic stenosis with evolving hypoplastic left heart syndrome (HLHS); HLHS with intact or restrictive atrial septum; and pulmonary atresia with intact ventricular septum, with concern for worsening right ventricular (RV) hypoplasia.

Fetal Cardiac Intervention in Critical Aortic Stenosis with Severe Mitral Regurgitation, Severe Left Atrial Enlargement, and Restrictive Foramen Ovale.

OBJECTIVE: To assess the intrauterine course and outcome of fetal cardiac intervention (FCI) in fetuses with critical aortic stenosis (CAS), severe mitral regurgitation (MR), severe left atrial dilatation (LAD), and restrictive foramen ovale (RFO) or intact atrial septum. METHODS: All fetuses with a prenatal diagnosis of CAS, severe MR, severe LAD, and RFO were retrospectively collected in one tertiary center for fetal medicine over a period of 10 years. Video recordings, pre- and postnatal charts were reviewed for cardiac and extracardiac anomalies, intrauterine course, and postnatal outcome. RESULTS: Nineteen fetuses with CAS, severe MR, severe LAD, and RFO were diagnosed in the study period. In 5 cases, FCI was not considered as the parents either opted for expectative management or for termination. In the remaining 14 fetuses, 21 FCI were performed: 14 balloon valvuloplasties, 2 atrioseptostomies, and 5 fetal atrial stent insertions. Seven of 14 fetuses (50%) had fetal hydrops, 5 of 14 fetuses (36%) presented with intact atrial septum. Procedure-related death occurred in 5 fetuses after aortic valvuloplasty or concomitant atrioseptostomy but in none after fetal atrial stenting. Due to progressive hydrops, two terminations of pregnancy were performed. Among the 7 live births, 3 died in the neonatal period. The remaining 4 received single ventricle palliation, 2 following fetal aortic valvuloplasty and 2 after fetal atrial stent insertion. CONCLUSIONS: CAS with severe MR, severe LAD, and RFO has a high overall mortality even in cases undergoing intrauterine intervention. Parameters that accurately predict the intrauterine and postnatal outcome have yet to be defined.

Cirurgias intrauterinas: alternativa de intervenção para as cardiopatias congênitas / Intrauterine surgeries: intervetion alternative for congenital cardiopathies

As cardiopatias congênitas são anormalidades estruturais ou funcionais do sistema cardiovascular, advindas desde o nascimento, mesmo que diagnosticadas posteriormente. Entre as malformações congênitas, as cardiopatias são as principais causas de mortalidade infantil nos Estados Unidos e em outros países desenvolvidos. Com o intuito de reduzir os efeitos progressivos dessas patologias, a intervenção intrauterina tem se destacado como opção terapêutica diante de resultados iniciais satisfatórios. O presente artigo teve por objetivo demonstrar a evolução da cirurgia intrauterina para correção cardíaca, a partir da avaliação dos benefícios ao feto e visando a riscos mínimos e aceitáveis para a mãe. Foi realizada uma pesquisa na base de dados Publisher Medline (PubMed), Scientific Electronic Library Online (SciELO) e Biblioteca Virtual da Saúde (BVS), incluindo artigos publicados entre 2008 e 2018; além da pesquisa efetuada no Manual de Medicina Fetal da SOGIMIG ­ 2018. Os critérios de elegibilidade são amplos. São necessários equipe multidisciplinar, equipamentos sofisticados e aperfeiçoamento da técnica, dessa forma dificulta-se a realização das cirurgias. Entretanto, diante dos resultados já demonstrados, a cirurgia intrauterina apresenta-se como alternativa terapêutica promissora.(AU)

The congenital cardiopathies are structural or functional abnormalities of the cardiovascular system, originated from birth, even when previously diagnosed. Among the congenic malformations, the cardiopathies are the main causes of infant mortality in the United States and in other developed countries. In order to reduce the progressive effects of these pathologies, intrauterine intervention has been highlighted as a therapeutic option in contempt of satisfactory initial results. This article has as goal to demonstrate the evolution of the intrauterine surgery for cardiac correction, based on the evaluation of the benefits to the fetus and aiming at minimum and acceptable risks to the mother. A research was made based on the Publisher Medline (PubMed) data base, Scientific Electronic Library Online (SciELO) and Biblioteca Virtual da Saúde (BVS), including published articles between 2008 and 2018. Beyond the research made on The fetal medicine manual from SOGIMIG ­ 2018. The eligibility criteria are broad. It is necessary a multidisciplinary team, sophisticated equipments and technique improvement, therefore interfering in the performance of surgeries. However, in contempt of the already demonstrated results the intrauterine surgery presents itself as a therapeutic promising alternative.(AU)

Outcomes of hypoplastic left heart syndrome and fetal aortic valvuloplasty in a country with suboptimal postnatal management.

BACKGROUND: Fetal aortic stenosis (AoS) may progress to hypoplastic left heart syndrome (HLHS) in utero. There are currently no data, prenatal or postnatal, describing survival of fetuses or neonates with AoS or HLHS in a country with suboptimal postnatal management. STUDY DESIGN: Prospective cohort study performed in Mexico, including cases diagnosed with AoS and HLHS within a 6-year period. AoS patients fulfilling previously published criteria for evolving HLHS (eHLHS) were offered fetal aortic valvuloplasty. Outcome variables were perinatal mortality, postnatal management, type of postnatal circulation, and overall survival. RESULTS: Fifty-four patients were included: 16 AoS and 38 HLHS. Eighteen patients had associated anomalies and/or an abnormal karyotype. Seventy-four percent of HLHS received comfort measures, with only three cases reporting an attempt at surgical palliation, and one survivor of the first stage. Fetal aortic valvuloplasty was performed successfully in nine cases of eHLHS. Overall postnatal survival was 44% in AoS with fetal aortic valvuloplasty, and one case (ongoing) in the HLHS group. CONCLUSIONS: HLHS in Mexico carries more than a 95% risk of postnatal death, with little or no experience at surgical palliation in most centers. Fetal aortic valvuloplasty in AoS may prevent progression to HLHS and in this small cohort was associated with ≈50% survival.

Fetal aortic valvuloplasty to prevent progression to hypoplastic left heart syndrome in utero.

Advances in fetal echocardiography have allowed for the prenatal diagnosis of congenital heart disease and an understanding of its natural history in utero. This insight has led to the development of fetal cardiac intervention (FCI) for select defects to prevent significant morbidity or mortality postnatally. Fetal aortic valvuloplasty (FAV) may be performed to prevent progression to hypoplastic left heart syndrome, a severe form of congenital heart disease, in utero. The current review focuses on this type of FCI and discusses the history of FAV, the rationale for intervention, candidate selection, procedural technique, and outcomes to date. Finally, the importance of building a multidisciplinary team to perform FCI is addressed.

Fetal cardiac intervention for right sided heart disease: Pulmonary atresia with intact ventricular septum.

Congenital heart disease (CHD), the most common of birth defects, can be serious enough to require a lifetime of medical care including multiple surgeries or other interventions. Advances in ultrasound technology and a better understanding of the progression of CHDs have made it possible to intervene in utero. This early stage intervention allows the still plastic cardiovascular system to return to a more normal trajectory thus sparing the newborn from negative consequences to morbidity and mortality. Fetal cardiac intervention (FCI) has been successful for the alleviation of left ventricular dysfunction resulting in remarkably positive outcomes for many families. Promising results support that FCI may also be useful in alleviating right ventricular dysfunction. This bodes well for expanding the use of FCI to lead to better postnatal adaptation and improved long-term function for more children with CHD.

Fetal and postnatal echocardiographic imaging of transposition of the great arteries with the aortic valve posterior to the pulmonary valve.

Transposition of the great arteries (TGA) with a posterior aorta is an uncommon but historically important variant of TGA. In this arrangement, the aorta is posterior to the pulmonary valve, maintains fibrous continuity with the mitral valve, and arises from the right ventricle. We present a case of fetal echocardiography demonstrating TGA with a posterior aorta. Postnatal transthoracic echocardiography and intra-operative assessment confirm the anatomy. To the best of our knowledge, this is the first published case of this anatomic lesion by fetal echocardiography.

In utero intervention for severe congenital heart disease.

The aim of foetal cardiac therapy is to treat an abnormality at the developmental stage so that the process of cardiac growth, which is complex and relies on the volume and direction of circulating blood as well as genetic determinants, can continue. In reality, most cardiac interventions are palliative; hence, major abnormalities are still present at birth. Nevertheless, tangible benefits following successful foetal intervention include improved haemodynamics and reduction in secondary damage leading to better postnatal outcomes. In cases of semilunar valve stenosis, or atresia, foetal valvuloplasty aims to achieve a biventricular, rather than univentricular, circulation. Opening and stenting a restrictive atrial foramen may preserve the pulmonary function in cases of hypoplastic left heart syndrome, thereby increasing the chances of successful postnatal surgery. More recent endeavours include percutaneous implantation of a miniaturised pacemaker to treat complete heart block and the promotion of left-sided heart growth by chronic maternal hyperoxygenation. The true clinical benefit of these interventions over natural history remains uncertain because of the paucity of appropriate randomised controlled trials (RCTs). Foetal cardiac therapy must now move from a pioneering approach to one that is supported by evidence, as has been done successfully for other foetal therapies.

Prenatal therapy for fetal cardiac disorders.

Fetal cardiac abnormalities are some of the commonest congenital disorders seen in prenatal life. They can be anatomical or functional and can develop de novo or as a consequence of either maternal or fetal disease. Untreated, morbidity and mortality rates are high for hypoplastic left heart disorders and for some fetal tachy and bradyarrhythmias. Optimum management strategies are often not clear because of the lack of knowledge about the precise natural history of some of these conditions. Prenatal therapy ranges from invasive fetal cardiac intervention to maternal administration of drugs for transplacental transfer to the fetus. This comprehensive review covers many fetal cardiac disorders and various prenatal therapeutic options that are available.