Fetal Cardiac Disease Research Articles

Fetal Surveillance in High-Risk Fetal Cardiac Disease: Frequency, Results and Relationship with Survival

ObjectivesWe hypothesized that pregnancies with high-risk fetal heart disease (FHD) would benefit from frequent prenatal surveillance, abnormal fetal surveillance results would be associated with worse outcomes, and cardiovascular profile scoring (CVPS) could identify FHD cases at highest risk of death. MethodsA retrospective single-centre study of all actively treated pregnancies with high-risk FHD from 2006–2020. Frequency and results of fetal surveillance, survival, and mode of delivery were collected. Frequent fetal surveillance was defined as ≥ once weekly fetal wellbeing testing commencing by 28–32 weeks of gestation, or from later diagnosis, until delivery. Where possible, the CVPS was calculated. ResultsFetal surveillance results were available in 92% (56/61) of pregnancies with high-risk FHD and were abnormal in 18% (10/56). A final CVPS of ≤7 carried a higher mortality (11/21, 52%) than ≥8 (6/31, 19% (P = 0.01)). There was a trend toward worse survival at last follow-up when fetal surveillance was abnormal versus normal (40%, 4/10 vs 72%, 33/46, P = 0.07). Survival did not differ between frequent versus infrequent surveillance (13%, 4/30 vs 3%, 1/31, P = 0.20); nor when comparing abnormal versus normal surveillance results (20%, 2/10 vs 7%, 3/46, P = 0.21). Where fetal surveillance was abnormal, emergency cesarean delivery was more common (70%, 7/10 vs. 4%, 2/46, P < 0.001). ConclusionAbnormal fetal surveillance results and/or a CVPS ≤7 may identify compromised fetuses with high-risk FHD who could benefit from altered management or expedited delivery. Given the high rates of abnormal fetal surveillance in high-risk FHD, frequent fetal surveillance in the third trimester should be considered.

Fetal Echocardiography From 10 to 15 Weeks of Gestation—Reliability, Genetic Associations, and Outcomes

There is increasing demand for accurate early fetal cardiac disease (FCD). We assessed the accuracy of early fetal echo (EFE) conducted in our high-volume fetal cardiac program and reviewed the spectrum of FCD, associated genetic anomalies, and outcomes encountered. We identified all EFEs performed from 10+0 to 15+6weeks of gestation from 2009 to 2021. We compared findings at EFE to fetal echo at ≥18+0weeks or autopsy and documented genetic testing results for all FCD cases. For those with discrepancy between EFE and later exam, the discrepancy impact was reviewed. A score was used to quantify the anatomy assessed. A total of 1,662 EFEs were performed in 1,387 pregnancies; all but 41 were considered diagnostic. Fetal cardiac disease was diagnosed at EFE in 130, including 101 major, 12 minor, 13 other FCD, and 4 arrhythmias. In 14/130 with FCD, endovaginal imaging was undertaken, which increased the score (1.6/9 vs 3.5/9; P=.049). Thirty-five of 130 had repeat EFE, which increased the score (5.2/9 vs 7.4/9, P<.0001). Fetal loss occurred before confirmation of FCD in 16 and termination in 64, and 11 were lost to follow-up. Thirty-nine had autopsy and/or fetal echo ≥18+0: 35 had FCD confirmed, and 4 had resolution. Of the 35 confirmed FCD, 27 had no, 7 minor, and 1 major change. Of 1,489 with normal EFE, later echo demonstrated FCD in 14: 3 major and 11 minor. In 16, FCD evolved, including 4 arrhythmias and 12 with progressive FCD. Sensitivity, specificity, and positive and negative predictive values of EFE in identifying major FCD were 92.9%, 100%, 100%, and 99.7%, respectively. In cases with FCD, 85.4% had genetic testing, of whom 71% (60.8% of the total) had abnormal results. In our experience, EFE permits accurate diagnosis and exclusion of most FCD. Endovaginal imaging and repeat EFE studies improved the ability to visualize structures adequately.

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia. Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders.

Machine Learning to Predict Outcomes of Fetal Cardiac Disease: A Pilot Study.

Prediction of outcomes following a prenatal diagnosis of congenital heart disease (CHD) is challenging. Machine learning (ML) algorithms may be used to reduce clinical uncertainty and improve prognostic accuracy. We performed a pilot study to train ML algorithms to predict postnatal outcomes based on clinical data. Specific objectives were to predict (1) in utero or neonatal death, (2) high-acuity neonatal care and (3) favorable outcomes. We included all fetuses with cardiac disease at Sunnybrook Health Sciences Centre, Toronto, Canada, from 2012 to 2021. Prediction models were created using the XgBoost algorithm (tree-based) with fivefold cross-validation. Among 211 cases of fetal cardiac disease, 61 were excluded (39 terminations, 21 lost to follow-up, 1 isolated arrhythmia), leaving a cohort of 150 fetuses. Fifteen (10%) demised (10 neonates) and 65 (48%) of live births required high acuity neonatal care. Of those with clinical follow-up, 60/87 (69%) had a favorable outcome. Prediction models for fetal or neonatal death, high acuity neonatal care and favorable outcome had AUCs of 0.76, 0.84 and 0.73, respectively. The most important predictors for death were the presence of non-cardiac abnormalities combined with more severe CHD. High acuity of postnatal care was predicted by anti Ro antibody and more severe CHD. Favorable outcome was most predicted by no right heart disease combined with genetic abnormalities, and maternal medications. Prediction models using ML provide good discrimination of key prenatal and postnatal outcomes among fetuses with congenital heart disease.

Initiating a Fetal Cardiac Program from Scratch in Low- and Middle-Income Countries: Structure, Challenges, and Hopes for Solutions.

Although fetal cardiac programs are well established in developed countries, establishing an efficient program in low- and middle-income countries (LMICs) is still considered a significant challenge. Substantial obstacles usually face the initiation of fetal cardiac service from scratch in LMICs. The primary structural frame of a successful fetal cardiac program is described in detail, emphasizing the required team members. The potential challenges for starting fetal cardiac services in LMICs include financial, awareness-related, prenatal obstetric screening, sociocultural, psychosocial, and social support factors. These challenges could be solved by addressing these barriers, such as collecting funds for financial support, raising awareness among families and health care providers, telemedicine, building international health partnerships, modifying training protocols for fetal cardiologists and sonographers, and initiating support groups and social services for families with confirmed fetal cardiac disease. Initiating a successful fetal cardiac program requires multi-aspect structural planning. The challenges for program initiation require diverse efforts, from modified training and promoting awareness of care providers and the community to governmental and nonprofit organizations' collaborations for proper building and utilization of program resources.

Correlação de Imagem Espaço-Temporal: Imagens Tridimensionais para Triagem Cardíaca Fetal e Avaliação de Doenças Cardíacas Congênitas

Correlação de Imagem Espaço-Temporal: Imagens Tridimensionais para Triagem Cardíaca Fetal e Avaliação de Doenças Cardíacas Congênitas

Spatio-Temporal Image Correlation: Three-Dimensional Imaging for Fetal Cardiac Screening and Congenital Heart Disease Assessment.

Spatio-Temporal Image Correlation: Three-Dimensional Imaging for Fetal Cardiac Screening and Congenital Heart Disease Assessment.

Cardiac problems in the fetus: a review for pediatric providers.

The aim of this study was to provide pediatric providers with a review of the diagnosis and management of fetal cardiac disease in the current era. Prenatal detection of congenital heart disease (CHD) has improved but is still imperfect. In experienced hands, fetal echocardiography can detect severe CHD as early as the first trimester and a majority of more subtle conditions in the second and third trimesters. Beyond detection, a prenatal diagnosis allows for lesion-specific counseling for families as well as for development of a multidisciplinary perinatal management plan, which may involve in-utero treatment. Given the diversity of cardiac diagnoses and the rarity of some, collaborative multicenter fetal cardiac research has gained momentum in recent years. Accurate diagnosis of fetal cardiac disease allows for appropriate counseling, pregnancy and delivery planning, and optimization of immediate neonatal care. There is potential for improving fetal CHD detection rates. Fetal interventions are available for certain conditions, and fetal and pediatric cardiac centers have developed management plans specific to the expected postnatal physiology.

Prenatal Diagnosis, Management, and Treatment of Fetal Cardiac Disease.

Prenatal diagnosis of congenital heart disease makes it possible to optimize and coordinate care of the fetus and pregnant person. Benefits encompass the full spectrum of pre- and perinatal care, from counseling to optimization of pregnancy care and fetal intervention. Prenatal diagnosis reduces the likelihood of postnatal hemodynamic compromise and improves long-term neurodevelopmental outcomes. Despite the benefits, prenatal diagnosis rates remain suboptimal, particularly for lesions that are not seen on standard 4-chamber imaging views. Improving prenatal diagnosis rates requires education and outreach efforts targeting community practices where most initial screening occurs.

How We Would Treat Our Own Hypoplastic Left Heart Syndrome Neonate for Stage 1 Surgery

ALTHOUGH NO LONGER UNIFORMLY fatal, hypoplastic left heart syndrome (HLHS) continues to significantly challenge providers across pediatric specialties. This is especially true in the neonatal period when patients with HLHS undergo stage 1 palliative surgery. Despite advances in medical and surgical management, in-hospital and 1-year mortality remain high. 1 Ohye RG Sleeper LA Mahony L et al. Comparison of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med. 2010; 362: 1980-1992 Crossref PubMed Scopus (686) Google Scholar , 2 Mahle WT Spray TL Wernovsky G et al. Survival after reconstructive surgery for hypoplastic left heart syndrome: A 15-year experience from a single institution. Circulation. 2000; 102: III136-III141 Crossref PubMed Google Scholar , 3 Forbess JM Cook N Roth SJ et al. Ten-year institutional experience with palliative surgery for hypoplastic left heart syndrome. Risk factors related to stage I mortality. Circulation. 1995; 92: II262-II266 Crossref PubMed Google Scholar , 4 Stasik CN Gelehrter S Goldberg CS et al. Current outcomes and risk factors for the Norwood procedure. J Thorac Cardiovasc Surg. 2006; 131: 412-417 Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar , 5 Hirsch JC Copeland G Donohue JE et al. Population-based analysis of survival for hypoplastic left heart syndrome. J Pediatr. 2011; 159: 57-63 Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar , 6 Tweddell JS Sleeper LA Ohye RG et al. Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type. J Thorac Cardiovasc Surg. 2012; 144: 152-159 Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar , 7 Best KE Miller N Draper E et al. The improved prognosis of hypoplastic left heart: A population-based register study of 343 cases in England and Wales. Front Pediatr. 2021; 9635776 Crossref Scopus (10) Google Scholar , 8 Piber N Ono M Palm J et al. Influence of shunt type on survival and right heart function after the Norwood procedure for aortic atresia. Semin Thorac Cardiovasc Surg. 2022; 34: 1300-1310 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar , 9 Karamlou T Diggs BS Ungerleider RM et al. Evolution of treatment options and outcomes for hypoplastic left heart syndrome over an 18-year period. J Thorac Cardiovasc Surg. 2010; 139: 119-126 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar , 10 Azakie T Merklinger SL McCrindle BW et al. Evolving strategies and improving outcomes of the modified Norwood procedure: A 10-year single-institution experience. Ann Thorac Surg. 2001; 72: 1349-1353 Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar , 11 Newburger JW Sleeper LA Gaynor JW et al. Transplant-free survival and interventions at 6 Years in the SVR trial. Circulation. 2018; 137: 2246-2253 Crossref PubMed Scopus (133) Google Scholar At present, there is limited evidence-based society guidance on the perioperative management of neonates with HLHS undergoing stage 1 palliation. 12 Donofrio MT Moon-Grady AJ Hornberger LK et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation. 2014; 129: 2183-2242 Crossref PubMed Scopus (694) Google Scholar Extracorporeal Membrane Oxygenation for Stage 1 Palliation: Early bridge to recovery rather than a late act of pure despairJournal of Cardiothoracic and Vascular AnesthesiaPreviewWe appreciate the article by Zaleski et al. as it describes in detail the challenging management of a patient with hypoplastic left heart syndrome (HLHS) undergoing stage I palliation (S1P) - one of the most demanding tasks in cardiac surgery and anesthesiology for congenital heart disease [1]. The course of the young patient presented in their article was uneventful. Nonetheless, internationally reported premature mortality is high at up to 14.3% and remains at 8-11% even in high-volume North American centers, and even after establishing specialized "single-ventricle” teams [2;3]. Full-Text PDF

Prenatal Detection of Congenital Heart Disease: Importance of Fetal Echocardiography Following Normal Fetal Cardiac Screening.

Fetal echocardiography may be performed because of noncardiac indications (the pregnancy is identified as high risk for fetal cardiac disease), or because of fetal cardiac indications (abnormal fetal heart at the time of a screening ultrasound). Considering recent improvements in fetal cardiac screening over the past decade, the goal of this single institution study was to reconsider the importance of performing fetal echocardiography purely for screening (noncardiac) indications. We performed a retrospective analysis to review screening and fetal cardiac indications and fetal cardiac findings for fetal echocardiograms performed at UCLA between 2015 and 2019. Fetal heart disease was identified in 391 (15%) of 2592 pregnancies in this study. Among these 391 cases, 227 (58%) occurred in low-risk pregnancies (without screening indications). While 79% of the cases of fetal cardiac disease were referred with fetal cardiac indications, 21% of the cases were referred with exclusively screening indications. Fetal cardiac disease was discovered on fetal echocardiograms in 4% of pregnancies referred for exclusively screening indications, but the frequency of fetal cardiac disease following normal fetal cardiac screening has decreased from 6% in 2015 to 3% in 2019. In our population, we recommend continued referral for fetal echocardiography for pregnancies identified as high risk for CHD. However, as fetal cardiac screening continues to improve, referral for fetal echocardiography following normal fetal cardiac screening will have diminishing value and yield.

Advances in the Prenatal Management of Fetal Cardiac Disease.

Advances in the field have improved the prenatal management of cardiovascular diseases over the past few decades; however, there remains considerable challenges in the approach towards patient selection as well as the applicability of available therapies. This review aims to discuss the current knowledge, outcomes and challenges for prenatal intervention for congenital heart disease.

Complete heart block in fetus – A rare combination of maternal autoimmune disorder and fetal structural cardiac disease – A case report and review of literature

Majority of rhythm disturbances detected by fetal echocardiography are self-limiting. Appropriate work up of dysrhythmias is essential to prevent further damage of fetal conducting system and to initiate fetal therapy thereby reducing fetal losses. 25 year old Primi, 31 weeks of gestation, no comorbidities, was referred to our Antenatal OPD as severe fetal bradycardia. Antenatal Fetal Echo revealed third degree heart block with no evidence of hydrops. Maternal serum workup revealed autoimmune etiology. Fetal therapy started and Pregnancy followed up weekly till term gestation to deliver an alive baby by vaginal delivery. Baby was diagnosed to have Large ASD with a large PDA having bidirectional shunt by paediatric cardiologist. Surgical management was done by PDA ligation and permanent pacemaker. Unfortunately, baby succumbed due to respiratory failure and sepsis, as it was high risk complete heart block with multifactorial causation. Fetal bradyarrhythmia need to be evaluated carefully both for maternal autoimmune disorders and intrinsic cardiac causes of fetus. This case is reported for its rarity of having both etiologies presenting together as third degree or complete heart block.

Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers

BackgroundExperimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro–mediated congenital heart block (CHB). ObjectivesHydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. MethodsThis multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon’s optimal approach. Anti-SSA/Ro–positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. ResultsBy intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). ConclusionsThese prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573)

Factors associated with long-term cardiac dysfunction in neonatal lupus

ObjectivesCardiac manifestations of neonatal lupus (NL) have been associated with significant morbidity and mortality; however, there is minimal information on long-term outcomes of affected individuals. This study was initiated to...

Nonimmune hydrops fetalis management from the perspective of fetal cardiologists: A single tertiary center experience from Egypt.

Despite advances in managing nonimmune hydrops fetalis (NIHF), perinatal mortality is still significant. Fetal cardiac failure eventually occurs regardless of etiology. However, no previous study has addressed NIHF from fetal cardiologists' perspective. Therefore, we evaluated etiology and management of a NIHF cohort requiring fetal cardiologist consultation in a developing country. A single-center retrospective cohort study of 70 cases with NIHF that were referred to a fetal cardiology unit over four years was performed. Demographics, etiologic diagnosis, and outcomes of the cases were assessed. Antenatal management was evaluated using cardiovascular profile score (CVPS). The most frequent diagnosis was Idiopathic hydrops 42(62.6%), followed by hydrops due to cardiac diseases 19(28.4%), and 3 dead fetuses were detected at the first fetal echocardiography. Treatment of fetal tachyarrhythmia (n = 7) had 100% success rate in terms of antenatal hydrops resolution. Digoxin was used in cases of structural heart diseases, twin- twin transfusion syndrome, and dilated cardiomyopathy with perinatal mortality occurring in all cases (n = 9). In cases of idiopathic hydrops, 14 fetuses received digoxin with intrauterine hydrops resolution in 2/14 (14%) while non-treated cases had intrauterine or early neonatal death. Nonimmune hydrops is the worst complication of diverse etiologies. Limitations in resources for advanced investigations in developing countries increase the possibility of categorizing NIHF as idiopathic. Tachyarrhythmia induced hydrops can be entirely reversed with antenatal therapy while non-tachyarrhythmia fetal cardiac disease outcomes are unfavorable regardless of therapy. On the other hand, idiopathic hydrops shows a limited potential response to digoxin in utero.

AIUM Practice Parameter for the Performance of Fetal Echocardiography.

AIUM Practice Parameter for the Performance of Fetal Echocardiography.

RAPID PROGRESSION TO COMPLETE HEART BLOCK IN A FETUS WITH ENDOCARDIAL FIBROELASTOSIS

Transplacental transfer of maternal anti-Ro/La antibodies (ab) can result in fetal cardiac disease, most commonly affecting the conduction system, but there can also be associated fibrosis of the myocardium and endocardium. Fetal echocardiogram was performed at 20 weeks in a healthy patient

A portable prototype for diagnosing fetal arrhythmia

Abstract Expert knowledge and proper techniques are necessary for diagnosing and treating fetal cardiac disease. Fetal arrhythmia represents an important part of fetal cardiac disease as it conveys abnormalities in the electrophysiological state of the heart. Arrhythmias can be caused by rate or rhythm alterations or by abnormalities in QRS or QT intervals. Fetal echocardiography has been the gold standard for pediatric cardiologists since it assesses multiple aspects of fetal cardiovascular pathology. In parallel, artificial intelligence techniques are being designed to provide additional support to experts in the medical field in terms of detection and accuracy. The present manuscript describes the development of a prototype meant to be an auxiliary for the detection of fetal arrhythmias by analyzing the fetal heart rate (FHR) and its variability. It consists of a portable electrocardiograph and a mobile application that, together, extract the fetal electrocardiogram for its analysis to finally render a first diagnosis. Conducted tests with synthetic signals based on clinical fetal arrhythmia provided a detection rate of 88.88%. Results from tests with pregnant women may indicate that the proposed prototype can be used to render a first diagnosis without entirely depending on expert assistance. This prototype might be helpful to perform routine check-ups in the second or third trimester in pathological pregnancies associated with high risk of onset/progression of fetal arrhythmias. In addition, medical practitioners could use it to corroborate a given diagnosis or in scenarios where there is an insufficiency of human experts to attend a high population of patients.

234: NAFTNET retrospective report on dexamethasone and fetal heart block

Complete atrioventricular block (CAVB) occurs in 1-2% of SSA positive pregnancies and the consequences are significant: approximately 20% die and 50% require permanent cardiac pacing by 1 year of age. We hypothesize that dexamethasone (DEX) treatment for fetal anti-SSA/SSB antibody-mediated cardiac disease leads to better pregnancy outcome. Therefore, we assessed recent era experience of treatment with DEX of pregnancies with SSA/SSB-mediated fetal cardiac disease including all degrees of heart block on pregnancy, neonatal outcome and complication rates. We performed a retrospective multi-center cohort study of all SSA/SSB antibody positive pregnancies with fetal conduction system disease reported to the participating NAFTNet centers between January 2010 through December 2017. The primary outcomes included preterm delivery, maternal comorbidities, neonatal complications and secondary outcomes were, need for a pacemaker < 28 days, heart transplantation in the 1st year of life, and intrauterine or neonatal death in maternal/fetal days treated with DEX versus managed expectantly. There was a total of 101 SSA/SSB positive pregnancies of which 75 were treated with DEX and 26 were not. Of those treated, 49/75 (65%) met the primary outcome including 37 premature deliveries; 12 mothers developed comorbidities during treatment (4 with fetal growth restriction, 4 with oligohydramnios, 2 with new or worsening gestational diabetes, and 6 with mood disturbances). In comparison, in the untreated group 11/26 (42%) met the primary outcome of premature delivery. Regarding secondary outcomes, 32/75 (43%) dexamethasone-treated fetuses either required a pacemaker or had a fetal demise/died by 28 days of life, while 13/26 (50%) untreated met the secondary outcome of requiring pacemaker placement or fetal demise/dying prior to 28 days of life, while 1 infant required listing for cardiac transplantation. While the use of dexamethasone in SSA and SSB positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was a similarly high rate in untreated SSA/SSB positive pregnancies suggesting that the maternal disease itself is influencing pregnancy complications. A trend suggesting that treatment decreases neonatal morbidity and progression of conduction disease deserves further study.