Perinatal Cardiology-Part 1

The in utero progression of congenital heart diseases (CHDs) can be observed in almost all CHDs during the first, second, and third trimesters of pregnancy. The progression of a cardiac disease can be associated with worsening of structural defects, new onset of foramen ovale restriction, decreased ventricular inflow or outflow, or worsening arch obstruction. The role of contemporary fetal cardiologists is to not only diagnose CHDs but also foresee the condition of the newborn after delivery and plan potential treatment in the first hours-or even minutes-of life. For this reason, pregnancy and delivery management of newborns with a prenatal diagnosis of CHD requires a multidisciplinary team composed of fetal and pediatric cardiologists, obstetricians and maternal–fetal specialists, neonatologists, and other pediatric specialists. The potential progression of CHD severity in utero and changes occurring during the transition from fetal life to infancy led to the creation of new classifications of CHDs dedicated to fetuses only. Severest heart defects are defined as CHDs in fetuses whose treatment results in death in nearly all cases, and potential treatment is needed immediately after birth; severe urgent heart defects are defined as CHDs in fetuses who need to undergo an invasive cardiologic treatment or cardiologic surgery within the first hours of postnatal life; severe planned heart defects are defined as CHDs in fetuses who need to undergo cardiologic surgery within the first month after birth, usually with ductal-dependent circulation and prostaglandin infusion to prolong prenatal physiology; and planned heart defects are defined as CHDs in fetuses who do not need to undergo cardiologic surgery within the first month after birth (usually surgery may be postponed to infancy). The only tool for the proper qualification of fetuses to one of the groups in the new classification system is fetal echocardiography.

An understanding of normal cardiovascular development is essential to appreciating the abnormalities seen in congenital heart disease. The cardiovascular system develops within the mesoderm and through the process of folding, and establishment of the body axis, patterning and laterality it transforms from blood islands into the primitive heart tube and then the complex cardiac structures that supply the fetus. This chapter will discuss the embryological formation of the cardiovascular system and how deviations from normal development result in common cardiac defects.

With increasing obesity and diabetes in our population, and alcohol, marijuana, and tobacco use among women of child-bearing years, there is a high probability of embryonic exposure to risk factors before pregnancy is recognized. These metabolic changes and environmental factors are known in animals to induce birth defects and specifically, congenital heart defects (CHDs). This study discusses an interrelationship between placental and heart development in which blood flow between these developing organs needs to be maintained at specific levels. When blood flow is altered in the mouse by embryonic exposure to environmental factors, dysmorphogenesis occurs. Additionally, with gene expression analysis of the embryonic heart it was demonstrated that with elevated homocysteine (HCy) a natural metabolite, and alcohol exposures, numerous Gene Ontology classifications relating to lipid metabolism were altered. As for example, relative to the female embryo, significantly more alterations occurred in the male embryonic heart transcriptome with homocysteine exposure. That lipid metabolism was altered was validated by staining for localization of neutral lipids in the embryonic mouse embryos. We demonstrated that lipid droplet amount and the localization patterning were changed with exposures in both the fetal four-chambered heart and in the placenta. More changes occurred, however, in the placental tissue. We have demonstrated that a regimen of high folic acid supplementation of the pregnant mouse diet started with the morning after conception prevented the environmentally induced alterations. The importance of lipids in trophoblast and placental development, the relationship to gender, and how folate supplementation normalizes development through epigenetic programming is reviewed.

The placenta is a complex organ with a distinct characteristic, it receives blood supplies from maternal and fetal circulation, forming two distinct, yet connected, systems: the maternal-placental (uteroplacental) blood circulation and the fetalplacental (fetoplacental) blood circulation. In the past decades, there have been considerable advances in the understanding of human placental circulatory physiology. Placental circulation is established early in pregnancy and adequate placental circulation and perfusion ensure that the fetus obtains an adequate supply of oxygen and nutrients. Placental vascularization involves the interaction of several regulatory pathways. Pregnancy-associated uterine vascular adaptions are the basis of the regulation of the maternal placental flow rate. Hemodynamic and structural changes ensure a low placental vascular resistance and normal umbilical blood flow which is suitable to supply oxygen and substrates needed to the fetus. This chapter reviews the structure of the human placental circulation and its development.

Congenital heart diseases are more common than chromosomal abnormalities or neural tube defects. Although been one of the cause of mortality in infants, early diagnosis of heart defects increases survival. It is of utmost importance to perform adequate cardiac screening. The International Society of Ultrasound in Obstetrics and Gynecology standardized the basic echocardiographic planes, in order to facilitate its use, increasing diagnosis. Therefore, in this chapter, we will discuss the anatomy and a systematized technical description of the fetal heart by two-dimensional (2D) echocardiography, emphasizing its indications, essential points for a good cardiac evaluation, and notions about some heart defects.

The role of first-trimester ultrasound has evolved from the measurement of crown-rump length (CRL), nuchal translucency (NT) and nasal bone to involve more detailed assessment of fetal anatomy. The majority of cardiac malformations are properly defined and potentially detectable by the time of the 11-13+6 week ultrasound examination. The sensitivity of ultrasound screening for cardiac abnormalities varies according to the marker being assessed (increased NT, tricuspid regurgitation, abnormal ductus venous flow), operator experience and the extent of a protocol for formal sequential structural assessment of the heart. All cardiac structures can be visualised from 13 weeks onwards. Early fetal echocardiography has been shown to be feasible and highly sensitive and specific in experienced hands. Early identification of cardiac abnormalities allows the assessment of chromosomal abnormalities/genetic syndrome at an early stage, giving parents more reproductive autonomy. Operators should be aware of the limitations of an early cardiac examination: Some lesions progress as pregnancy advances and there is still a need for a follow up ultrasound at 20 weeks’ gestation.

Fetal arrhythmias are rare but they are an important avoidable cause of perinatal mortality. Timely diagnosis is therefore crucial, as treatment can be life saving. Careful evaluation of cardiac structure and function using different echocardiographic modalities can exclude structural cardiac anomalies as well as provide accurate information about the atrial and ventricular contraction rates, their relationship, conduction pattern and hemodynamic consequences of arrhythmia. Although observation and reassurance will suffice in a substantial proportion of pregnancies complicated by fetal arrhythmia, some will require intrauterine therapy or early delivery followed by postnatal treatment to prevent heart failure and fetal/neonatal demise. Fortunately, most common fetal arrhythmias are few of those conditions that can be managed successfully in utero with good results. In this chapter, we describe the normal and abnormal fetal cardiac rhythms, their diagnosis and prenatal management.

Cardiac position refers to the physical location of the heart relative to the thorax irrespective of cardiac axis. Deviation from its normal location can be due to extrinsic factors, embryologic defects, or as a result of structural cardiac abnormalities. In cardiology, situs refers to the position, arrangement and orientation of the various organs found in the abdomen (visceral) and thorax (atrial situs). In general, more complex congenital heart diseases (CHD) are associated with abnormalities of the situs such as situs ambiguous (isomerism or ‘heterotaxy’). The heterotaxy syndrome has been linked to mutations of different genes and environmental factors (e.g. diabetes and retinoic acid exposure in utero) during the establishment of left-right asymmetry within earliest embryonic stages. Left atrial isomerism is associated with complete heart block and an increased risk of fetal hydrops, leading to poor in utero outcome. Conversely, right isomerism results in poorer postnatal outcomes since anomalous pulmonary venous return and complex cardiac anomalies are common findings in such cases. Prenatal diagnosis of cardiac position and situs abnormalities by cardiac ultrasound echocardiography can help guide recommendations concerning in utero and postnatal outcome.

The frequency of the different fetal septal defects and their presentation prenatally is described, including atrial septum defects (ASDs), ventricular septum defects (VSDs) and atrioventricular septum defects (AVSDs). Embryology of the defects and the association with underlying aneuploidy and genetic syndromes are discussed. Image findings in the fetal period are presented alongside diagrams to aide comprehension of the ultrasound views. A brief summary of prognosis and postnatal course of these conditions is also included.

The fetal right heart malformations are a heterogeneous group of anomalies that basically involve the tricuspid and pulmonary valves. Ebstein´s anomaly usually consists of the existence of a downward displacement of the insertion of the septal and posterior leaflets of the tricuspid valve. Tricuspid dysplasia is an abnormality of the chordae tendinae and/or the leaflets, which are thickened, of a normally inserted tricuspid valve. Both conditions are characterized by an incomplete closure of the valve in systole, causing tricuspid regurgitation that may cause cardiomegaly, heart failure and hydrops. Chromosomal defects are rare and the mortality for prenatally detected forms is high, with survival rates at 5 years less than 25%. In tricuspid atresia there is a replacement of the valve by a fibromuscular tissue and is almost always associated with a ventricular septal defect. The right ventricle is invariably hypoplastic, and in up to 25% of cases there is ventriculo-arterial discordance. Chromosomal abnormalities are rare, and the outcome is usually good, with survival rates at 20 years of 61-75%. In mild to moderate forms of pulmonary stenosis, the pulmonary valve appears thickened and/or narrowed, and is visible continuously throughout the cardiac cycle. The fourchamber view is usually normal. On color Doppler, there is high-velocity turbulent flow across the pulmonary valve. The outcome is good in most cases. In severe forms of pulmonary stenosis or pulmonary atresia with intact ventricular septum there is an almost complete obstruction of the right ventricle outflow tract due to severe dysplasia or complete absence of the pulmonary valve, respectively. This can be assessed both in B-mode and with color Doppler. The only route for blood supply to the lungs is the ductus arteriosus. Depending on the tricuspid valve, the right ventricle can be severely small or normal sized, which has a paramount importance on the final outcome. Acquired forms of premature closure of the ductus arteriosus can be idiopathic or secondary to the administration to the mother of some medical treatments. It often appears abruptly, in the third trimester of pregnancy. The Doppler study shows an acceleration of the transductal flow, with a peak systolic velocity greater than 140 cm/s, a diastolic peak greater than 35 cm/s, and a pulsatility index lower than 1.9 m/s. When the closure is complete, there is an asymmetric cardiomegaly because of dilatation of the right chambers, right ventricle hypertrophy and dilatation of the pulmonary artery and branches, while the duct is narrowed.

Congenital heart defects (CHDs) represent the most common congenital malformations, especially those affecting the left side of the fetal heart. During fetal life, the presence of the ductus arteriosus is responsible for the low intrauterine mortality rate if compared with the postnatal life. Prenatal diagnosis of CHDs has improved over the past 20 years and diagnostic enhancement has been obtained with the introduction of standardized examination of the fetal heart together with the technological advancement of the ultrasound equipment, particularly with the introduction of the four-dimensional (4D) ultrasound technique based on spatiotemporal- image correlation (STIC) or the application of the three-vessels and trachea view (3VT). The chapter describes and reports the evolution of the antenatal detection of left cardiac malformations, with emphasis regarding the echocardiographic characteristics that need to be evaluated in order to assess the hemodynamic state of the fetus. An extending search and analysis of the medical literature has been sought and describe in relation to the prenatal ultrasound diagnosis of aortic coarctation (CoA), aortic stenosis (AS), interrupted aortic arch (IAA), hypoplastic left heart syndrome (HLHS), aortic arch abnormalities and aorto-pulmonary window (APW). Understanding the cardiac performance of the fertus is of vital and critical importance to plan appropriate management and prognosis. Cardiac defect as critical aortic stenosis (CAS), IAA and HLHS are described as a potential emerging pathogenetic continuum. Attention has been paid to the latest improvement of in utero surgery and technique such as fetal aortic valvuloplasty in case of CAS or severe CoA and the use of multiple scoring system to predict postnatal biventricular circulation are described in great details. Notewithstanding, the chapter is enriched by a series of 2D- as well as 3D/4D ultrasound imaging and videos for each type of left cardiac malformation.

Conotruncal anomalies are characterized by abnormalities of the great vessels of the heart. There are five types of conotruncal anomalies named as tetralogy of Fallot, double outlet of the right ventricle, transposition of the great arteries, truncus arteriosus and corrected transposition of the great arteries. These lesions known as “conotruncal anomalies” are caused by aberrant development of the conotruncal region of the embryonic heart. Prenatal diagnosis of congenital heart disease optimizes obstetric and neonatal care. Identification of these anomalies in prenatal life allows a variety of treatment with options to be considered, including delivery at a tertiary center, termination of pregnancy in some cases and in utero therapy. Majority of fetuses with conotruncal anomalies will undergo surgery in the neonatal period or in the first year of life. This chapter will discuss the fetal echocardiographic findings, extracardiac and chromosomal anomalies associations, prenatal and postnatal outcomes of conotruncal anomalies.

The normal left aortic arch courses from the ascending aorta to the left, upwards and backwards in relation to the trachea. The aortic arch branches into the right innominate, left common carotid and the left subclavian artery in sequence. The aortic arch is divided into the proximal transverse arch and the distal transverse arch and the aortic isthmus. Abnormalities of the aortic arch involve obstructive lesions, e.g. coarctation of the aorta, and abnormalities of branching and position of the aortic arch and the latter are topic of this article. Branching and position abnormalities of the aortic arch have clinical meanings: mechanical compression of airway and esophagus by forming a vascular ring or sling, association with cardiac abnormalities, and association with chromosomal abnormalities. This chapter describes anatomical, genetical and echocardiographic features as well as clinical postnatal implications of abnormalities of branching and position of the aortic arch.