Fetal Cardiac Disease Research Articles

Understanding the Limitations of Fetal Cardiac Imaging

Congenital heart defects are among the most common fetal structural malformations, with a prevalence of 8 in 1,000 live births, and are a significant source of infant mortality. Women with low-risk pregnancies are screened for fetal cardiac disease by anatomical ultrasonographic surveys. Fetal echocardiography is typically reserved for pregnant women with a suspected fetal cardiac lesion based on fetal survey and pregnancies at high risk for fetal congenital heart defects. Prenatal diagnosis allows for collaboration and consultation with multiple services, improved recognition of associated extracardiac anomalies, and early detection of underlying genetic anomalies. Theoretically, prenatal diagnosis should offer opportunities to improve postnatal management and long-term outcomes. However, the evidence to suggest benefit to prenatal diagnosis is mixed and the benefit seems to be dependent on the specific cardiac lesion. To facilitate the appropriate utilization of fetal echocardiography, it is necessary to understand how the study is currently being performed, its cost considerations, and how clinicians and sonographers can use it effectively to ensure appropriate image acquisition and interpretation.

Clinical yield of fetal echocardiography for suboptimal cardiac visualization on obstetric ultrasound.

Suboptimal cardiac imaging on obstetric ultrasound is a frequent referral indication for fetal echocardiography, even in the absence of typical risk factors for fetal cardiac disease. The clinical profile of patients and findings of examinations performed for such an indication are not well defined. Given the increased cost, time and resource utilization of fetal echocardiography, we sought to determine the clinical findings of such referrals. We performed a single-center review of such referrals from January 2010 to June 2016. Patients with commonly accepted indications for fetal echocardiography were excluded. Demographic variables and echocardiogram findings were collected. Findings were classified as (1) "normal," (2) "probably normal," if minor pathology could not confidently be excluded, or if minor findings were noted that were expected to resolve, or (3) "abnormal." Rates of pathology were determined with comparison of nonobese and obese populations. A total of 583 gestations in 562 women were included (median gestational age 23.3 weeks, range 19.0-38.4). The median body mass index (BMI) was 34.6 kg/m2 (range 17.2-66.3 kg/m2 ). The majority of women were obese (BMI ≥ 30 kg/m2 in 74.6%). Overall, 574 of 583 examinations (98.5%) were normal or "probably normal." Pathology was noted in 9 fetuses (1.5%), 3 of whom required intervention (0.5%). No ductal dependent lesions were diagnosed. There was no significant difference in pathology rates between nonobese and obese mothers. We found a low fetal cardiac anomaly rate in studies performed for suboptimal views on obstetric ultrasound. The majority of women referred for this indication were obese. The practice of routine referral for this indication deserves further evaluation.

Prevention and treatment in utero of autoimmune-associated congenital heart block.

Transplacental transfer of maternal anti-Ro and/or anti-La autoantibodies can result in fetal cardiac disease, including congenital heart block and cardiomyopathy, called cardiac neonatal lupus (NL). Thousands of women are faced with the risk of cardiac NL in their offspring, which is associated with significant morbidity and mortality. There are no known therapies to permanently reverse third-degree heart block in NL, although several treatments have shown some effectiveness in incomplete heart block and disease beyond the atrioventricular node. Fluorinated steroids taken during pregnancy have shown benefit in these situations, although adverse effects may be concerning. Published data are discordant on the efficacy of fluorinated steroids in the prevention of mortality in cardiac NL. β-agonists have been used to increase fetal heart rates in utero. The endurance of β-agonist effect and its impact on mortality are in question, but when used in combination with other therapies, they may provide benefit. No controlled experiments regarding the use of plasmapheresis in cardiac NL have been performed, despite its theoretical benefits. Intravenous immunoglobulin was not shown to prevent cardiac NL at a dose of 400 mg/kg, although it has shown effectiveness in the treatment of associated cardiomyopathy both in utero and after birth. Retrospective studies have shown that hydroxychloroquine may prevent the recurrence of cardiac NL in families with a previously affected child, and a prospective open-label trial is currently recruiting patients in order to fully evaluate this relationship.

Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association.

The goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease. A writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine. Recommendations relating to the specifics of fetal diagnosis, including the timing of referral for study, indications for referral, and experience suggested for performance and interpretation of studies, are presented. The components of a fetal echocardiogram are described in detail, including descriptions of the assessment of cardiac anatomy, cardiac function, and rhythm. Complementary modalities for fetal cardiac assessment are reviewed, including the use of advanced ultrasound techniques, fetal magnetic resonance imaging, and fetal magnetocardiography and electrocardiography for rhythm assessment. Models for parental counseling and a discussion of parental stress and depression assessments are reviewed. Available fetal therapies, including medical management for arrhythmias or heart failure and closed or open intervention for diseases affecting the cardiovascular system such as twin-twin transfusion syndrome, lung masses, and vascular tumors, are highlighted. Catheter-based intervention strategies to prevent the progression of disease in utero are also discussed. Recommendations for delivery planning strategies for fetuses with congenital heart disease including models based on classification of disease severity and delivery room treatment will be highlighted. Outcome assessment is reviewed to show the benefit of prenatal diagnosis and management as they affect outcome for babies with congenital heart disease. Fetal cardiac medicine has evolved considerably over the past 2 decades, predominantly in response to advances in imaging technology and innovations in therapies. The diagnosis of cardiac disease in the fetus is mostly made with ultrasound; however, new technologies, including 3- and 4-dimensional echocardiography, magnetic resonance imaging, and fetal electrocardiography and magnetocardiography, are available. Medical and interventional treatments for select diseases and strategies for delivery room care enable stabilization of high-risk fetuses and contribute to improved outcomes. This statement highlights what is currently known and recommended on the basis of evidence and experience in the rapidly advancing and highly specialized field of fetal cardiac care.

The Role of Fetal Echocardiography in the Assessment of Fetal Aneuploidy

Advances in both imaging technology and understanding of fetal cardiac disease have contributed to a dramatic increase in the sensitivity and specificity of fetal echocardiography over the last few decades. Fetal echocardiography now plays an important role in the prenatal evaluation of fetuses with known or suspected aneuploidy. In this article, specific situations in which fetal echocardiography has a part in noninvasive aneuploidy screening algorithms are discussed.

P10.08: Accuracy of ultrasound findings in fetal cardiac disease correlated with neonatal diagnosis

P10.08: Accuracy of ultrasound findings in fetal cardiac disease correlated with neonatal diagnosis

Prenatal Evaluation and Management of Fetuses Exposed to Anti-SSA/Ro Antibodies

Maternal anti-SSA antibodies are common, existing in up to 2 % of the general population. Fetuses exposed to these antibodies are at risk for both cardiac and noncardiac complications. The cardiac complications include arrhythmias, structural disease, and cardiomyopathy. Although rare, the cardiac disease associated with these antibodies is permanent and severe. Current fetal echocardiographic screening tools are nonspecific. The type and frequency of screening needed is controversial. Although promising transplacental treatment strategies exist, prospective randomized studies are lacking. Dexamethasone, the medication used most frequently, imposes significant risks to both mother and fetus. This report presents a discussion of the at-risk population, the spectrum of fetal cardiac disease associated with maternal anti-SSA antibodies, the current fetal echocardiographic screening tools, the therapeutic options, and the management and delivery planning strategies. With appropriate prenatal follow-up, assessment, and delivery planning, even high-risk fetuses can be delivered safely and managed effectively.

Fetal heart disease and interruption of pregnancy: factors influencing the parental decision‐making process

To identify factors influencing parental decision when a fetal cardiac disease is diagnosed. All pregnancies with fetal cardiac abnormalities diagnosed at three academic hospitals of Marseille, France, between 2004 and 2008, were retrospectively studied. The association between maternal and fetal variables (maternal age, parity, ethnicity, gestational age at diagnosis, nuchal translucency, fetal gender, chromosomal and extra cardiac abnormalities, and severity of the cardiopathy) and parental decision was tested using univariate and multivariate statistical methods One hundred eighty-eight cases of fetal cardiac disease were analysed, of which 63 were interrupted pregnancies (IP) and 125 continued pregnancies (CP). Four factors were important in the parental decision-making process: the severity of cardiac malformation, the ethnic origin of the parents, the gestational age at diagnosis and the chromosomal abnormalities. Counselling of parents following the diagnosis of a congenital heart disease should take into account that, in addition of the severity of the congenital heart disease (CHD), ethnicity, gestational age at diagnosis and chromosomal abnormalities influence parental decision regarding pregnancy continuation or interruption.

Spontaneous Rupture of Atrioventricular Valve Tensor Apparatus as Late Manifestation of Anti-Ro/SSA Antibody-Mediated Cardiac Disease

Atrioventricular (AV) block and endocardial fibroelastosis associated with dilated cardiomyopathy are the most common clinical manifestations of anti-Ro/SSA-mediated fetal cardiac disease. Valvar dysfunction has not been a prominent feature of this disease; however, recent anecdotal cases have suggested an association between rupture of the AV valve tensor apparatus and maternal anti-Ro/SSA antibodies. In the present study, we have described the clinical and laboratory findings and reviewed the published data for infants of anti-Ro/SSA-positive pregnancies with AV valve insufficiency due to chordal rupture from the papillary muscles. The histopathologic features of the papillary muscle and ventricular free wall and septum biopsy specimens were examined and compared to the sections of AV leaflets from 6 autopsied fetuses with anti-Ro/SSA-mediated complete AV block without chordal disruption. Specific epitopes to the p200 region of Ro52, and Ro60 antibodies were evaluated in cases with chordal rupture. Severe AV valve insufficiency was detected prenatally (as early as 34 weeks of gestation) or postnatally (as late as 182 days) after areas of patchy echogenicity were noted in the papillary muscle at 19 to 22 weeks of gestation. Postnatally, urgent valve surgery was performed in 5 of 6 patients; 1 of 6 patients died preoperatively. All patients tested positive for Ro52. Valve leaflet tissue from the autopsy specimens was normal. The ventricular free wall and septum biopsy specimens from a patient with chordal rupture showed normal tissue; however, the papillary muscle biopsy specimens demonstrated severe atrophy with near total replacement of myocytes by fibrosis and dystrophic calcifications, and negative immunochemistry findings. In conclusion, these findings have defined an underappreciated complication of fetal antibody-mediated cardiac inflammation.

The Fetus as a Cardiac Patient: Assessment and Therapy of Cardiovascular Pathology before Birth

The past few decades have seen major advances in evaluation and treatment of fetal cardiovascular diseases. Largely due to advances in imaging, recognition of structural pathology in the developing human heart can now be performed as early as the 12th week of pregnancy and can be seen to develop and progress through gestation. Because of the observation that serious structural congenital heart disease may progress from seemingly minor disease if untreated, several centers are now intervening before birth to address such abnormalities and attempt to prevent the further development of structural disease. Furthermore, detailed assessment of cardiac rhythm, function, and myocardial mechanics is now also possible as early as the first trimester. Transplacental treatment for fetal rhythm abnormalities has dramatically changed the outcomes for affected pregnancies in the past decade. More recently, several centers have begun to incorporate routine fetal cardiovascular assessment in the evaluation of diseases such as congenital cystic adenomatiod malformation of the lung, twin-twin transfusion syndrome, and congenital diaphragmatic hernia where structural disease may impose significant comorbidity postnatally, and hemodynamic derangements and functional pathology secondary to the primary process may impact the fetus in utero. Recognition of potentially treatable fetal cardiac disease may alter the prognosis for these patients in the perinatal period as in utero treatment to address the primary abnormality has been shown to improve the hemodynamic derangements observed. Finally, prenatal recognition of fetal cardiac disease in general may be changing the natural history and incidence of disease in the postnatal population. Regardless of training and background, any healthcare professional involved in the diagnosis and management of diseases of the fetus and newborn now needs to be cognizant of the potential contribution of prenatal cardiac assessment and treatment in the congenitally malformed or unwell fetus. In this special issue on the fetus as a cardiac patient, we have invited a few papers addressing issues unique to this patient group. The first paper of this special issue addresses ethical issues relating to fetal diagnosis of a major abnormality with special emphasis on cardiac malformations. Presented are discussions of the ethical concept of beneficence and the principle of patient autonomy in the context of counseling expectant mothers and the complex ethical situation which arises in the consideration of the fetus as a patient. The second paper presents a comprehensive review of cardiac findings in twin-to-twin transfusion syndrome (TTTS), a condition which is a severe complication of monochorionic twin pregnancy. TTTS is characterized clinically on ultrasound by polyhydramnios in the “recipient” twin and oligohydramnios in the “donor” with varying degrees of cardiac dysfunction in the recipient. The pathophysiology of the syndrome itself and of the development of cardiomyopathic changes remains incompletely understood. The review discusses what is known with respect to the cardiac findings at presentation, natural history, and response to treatment and discusses current approaches to a comprehensive cardiac evaluation of affected fetuses. The third paper describes a large series of fetuses presenting with findings consistent with cardiomyopathy or myocarditis and represents a large natural history study of these entities, underlining the particularly high perinatal loss rate with diagnosis of dilated cardiomyopathy or myocarditis, as opposed to many of the hypertrophic myopathies. The issue concludes with two thought-provoking review articles regarding the intrauterine environment and the complex interaction the developing fetal brain and circulatory system have with each other and the placental circulation. In the first of these, the authors present a discussion of intrauterine hypoxia, its various causes, and mechanisms whereby disease in the fetus may result. The final paper presents a comprehensive review of the current understanding of pathologic findings in the developing brain of the fetus and infant with congenital heart disease. Methods for detection, potential etiologies, and implications for neurodevelopmental outcome are discussed. Intriguing speculation regarding the possibility of altering the natural history of developmental brain abnormalities via in utero intervention will leave the reader eagerly anticipating future developments in the rapidly advancing field of fetal cardiovascular assessment and treatment. Anita J. Moon-Grady Shinjiro Hirose Greg Kesby Samuel Menahem Wayne Tworetzky

An expanded phenotype of maternal SSA/SSB antibody-associated fetal cardiac disease

Objectives. Conventional manifestations of fetal Sjögren's antibodies (SSA/SSB) associated cardiac disease include atrioventricular block (AVB), transient sinus bradycardia, endocardial fibroelastosis (EFE) and dilated cardiomyopathy. We describe other manifestations of cardiac disease.Methods. We describe three fetuses with unique myocardial and conduction system disease.Results. One had isolated EFE with subsequent mitral and tricuspid valve chordal avulsion, the second had sinoatrial and infrahissian conduction system disease, and in both, neonatal progression to life threatening disease occurred. The third had sinus node dysfunction and atrial flutter.Conclusion. These findings expand the clinical phenotype of maternal SSA/SSB antibody associated fetal cardiac disease.

406: SSA/SSB antibody mediated fetal cardiac disease with normal AV conduction

406: SSA/SSB antibody mediated fetal cardiac disease with normal AV conduction

ISUOG consensus statement: what constitutes a fetal echocardiogram?

In 2006 the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published practice guidelines for the sonographic screening of congenital heart disease (CHD) during the second trimester of pregnancy1. This document described two levels for screening low-risk fetuses for heart anomalies. Firstly, a ‘basic’ scan should be performed by analyzing a four-chamber view of the fetal heart. Secondly, an ‘extended-basic’ scan further examines the size and relationships of both arterial outflow tracts. The term ‘fetal echocardiogram’ was also mentioned as a more detailed sonographic evaluation to be performed by specialists in the prenatal diagnosis of CHD. Although common indications and imaging techniques were briefly discussed, it was thought important to further explain how this advanced diagnostic procedure differs from the basic and extended-basic cardiac screening examinations. A Fetal Echocardiography Task Force was subsequently asked to develop a standard description of ‘what constitutes a fetal echocardiogram’. Our original goal was to develop guidelines for a detailed examination of the fetal heart that were based on the literature and a consensus opinion of an expert panel. However, we soon realized that this project was quite different from developing minimum practice guidelines for fetal cardiac screening. There are several imaging modalities that can be used to evaluate fetal heart anomalies, ranging from M-mode techniques and color Doppler sonography to the use of four-dimensional (4D) ultrasonography with spatiotemporal image correlation (STIC). Consequently, our original efforts to develop a minimum practice guideline for fetal echocardiography evolved into a consensus statement that covers the following topics:

Standardization of the PQRST Waveform and Analysis of Arrhythmias in the Fetus Using Vector Magnetocardiography

Fetal magnetocardiography (fMCG) is useful for analysis of fetal cardiac events. However, fetal presentation and movement affect the fMCG waveform, making it difficult to standardize the waveform. The aim of this study was to investigate whether the use of vector magnetometers can compensate for these limitations. We studied 59 fetuses (gestational age, 22-40 wk, median, 32), including 41 with uncomplicated pregnancies and 18 with fetal cardiac disease. fMCG was recorded twice in each case, and the two waveforms were compared with each other in uncomplicated subjects to investigate the effects of fetal presentation. The superconducting quantum interference device (SQUID) system used in this study was a 12-channel vector magnetometer, by which the three components of the magnetic field (Bx, By, Bz) could be detected simultaneously at four recording points. By constructing the three components, a composite waveform (Bxyz) was obtained. The configuration of the composite waveforms was similar among normal fetuses always with positive polarity, independent of fetal presentation and movement. The difference in the time intervals (PR, QRS, and ventricular activation time [VAT]) between the first and second measurements was minimal in the composite waveforms (Bxyz) compared with that in each channel (Bx, By, Bz). Even before signal averaging, waveforms with high time resolution were recorded in at least one of the three components, making it possible to analyze fetal arrhythmias precisely. Our results indicate that vector magnetocardiography is potentially useful for standardization of the fMCG waveforms and to provide a more complete and accurate analysis of fetal arrhythmias.

In‐utero intervention for hypoplastic left heart syndrome — a perinatologist's perspective

.Today,whenHLHSisdiagnosedinthenewborn,or suspected by prenatal ultrasound studies, surgicalinterventions typically take one of two directions – eitherthe multistaged reconstruction pioneered by Norwood toenable single ventricle survival or cardiac transplantation.Compassionate care, although increasingly controversial,remains an option in some centers. Although increasingsurvival rates following both multi-staged surgery ortransplant are being reported, the nature of theseinterventions is such that these children remain at lifelongrisk for cardiac and neurologic morbidity.Consideration of HLHS as a candidate for

The influence of prenatal diagnosis on postnatal outcome in patients with structural congenital heart disease

Examination of the fetal heart has become an established part of mid-trimester anomaly scanning. Along side this has emerged the ability to diagnose congenital heart disease in the fetus with accuracy. Despite this, the development of screening programmes to look for fetal cardiac disease has only been partially successful. Furthermore, when detected, there seems to be little survival advantage associated with prenatal diagnosis. Demonstrating such an advantage is complicated by the nature of fetal cardiac disease, which tends to be severe and is often associated with extra-cardiac abnormalities. More selective studies, mostly involving small numbers of cases, are now beginning to demonstrate both improved survival and reduced morbidity in prenatally diagnosed infants presenting to cardiac intensive care units compared to those with a postnatal diagnosis.

New fetal cardiac imaging techniques

Rapid advances in graphics computing and micro-engineering have offered new techniques for prenatal cardiac imaging. Some of them can be non-invasively applied to both clinical and laboratory settings, including dynamic three-dimensional echocardiography, myocardial Doppler imaging, harmonic ultrasound imaging, and B-flow sonography. With clinical constraints, a few others have been mainly used in laboratories, such as endoscopic ultrasound, magnetic resonance imaging and biomicroscopy. Appropriate use and co-use of these new tools will not only provide unique information for better clinical assessment of fetal cardiac disease but also offer new ways to improved understanding of cardiovascular development and pathogenesis.

Introduction to Fetal Echocardiography

Fetal echocardiography is used to diagnose or exclude cardiac disease before birth. Fetuses known to be at risk for cardiac anomalies may be methodically screened; other fetuses present with abnormalities as pregnancy progresses and are studied as they are discovered. Abnormalities of anatomy as well as function may be detected. Anatomic abnormalities are often associated with additional noncardiac or chromosomal defects. Fetal cardiac disease may progress as gestation advances. Signs of deterioration include cardiac dilatation, increasing valvular insufficiency, and hydrops. Detection of fetal cardiac abnormalities allows the management team to better prepare for possible complications of labor and delivery and, in some cases, allows for treatment before birth.

In utero sonographic appearance of the atrial septum primum and septum secundum.

We present our observation of the sonographic appearance of the septum primum and septum secundum. The septum primum, as the valve of the foramen ovale, has been previously described as a mobile, echogenic line or dot in the left atrium. We believe that these previous descriptions recognize only a small part of a more complex three-dimensional shape. We studied 14 ideal patients, none of whom were referred for suspected fetal cardiac disease. In 1 case the septum primum was seen as a flaplike structure and in 8 cases as a circular structure. In 5 cases it was seen as both flaplike and circular, depending on the scan plane selected. A three-dimensional description of the shape of the septum primum, based on the work of Crelin, is proposed, which explains these two appearances. A better understanding of this anatomical feature may prevent mistaking the septum primum for an abnormality and provide the basis for future advances in fetal echocardiography.

Cardiac ultrasound: its role in the recognition and management of fetal heart disease.

This article briefly reviews the role of ultrasound scanning in the diagnosis and management of fetal cardiac disease. Currently, the potential exists for the accurate identification of a wide range of cardiac defects and for the diagnosis and successful management of many cardiac rhythm disturbances. Considerable benefit is derived for families with previously affected children when a normal fetal cardiac ultrasound report can be provided.