Chapter 1 Introduction
Formulation of the Problem
Prenatal diagnoses have been possible for more than 25 years.2 At about embryonic day 20 in the human fetus, progenitor cells within the mesoderm become committed to a cardiogenic destination.3 Most malformations compatible with 6 months of intrauterine life permit live offspring at term. A given malformation may exist in relative harmony with the fetal circulation, only to be modified considerably, at least physiologically, by dramatic circulatory changes at birth.4 Weeks, months, or years may then elapse before an anomaly reveals itself as characteristic or typical. A functionally normal aortic valve that is congenitally bicuspid at birth may take decades to fibrose, calcify, and present as overt aortic stenosis. Conversely, a malformation may disappear, as is the case with spontaneous closure of a ventricular septal defect.
Congenital malformations of the heart and circulation are not fixed anatomic defects that appear at birth but instead are anomalies in flux that originate in the early embryo, evolve during gestation, survive the dramatic circulatory alterations at birth, and change considerably during the course of extrauterine life. Congenital heart disease was once the exclusive and legitimate domain of pediatrics, but survival patterns have changed appreciably.5,6 In the United States today, there are more adults with congenital heart disease than there are infants and children; these new generations of patients are best cared for by specially trained cardiologists.7 Clinical presentations, especially in adults,8,9 can be exceptionally complex.10–12
Furthermore, certain defects that are actually or potentially of functional significance are not gross structurally, such as congenital complete heart block, either isolated (see Chapter 4) or with congenitally corrected transposition of the great arteries (see Chapter 6) or left isomerism (see Chapter 3); Wolff-Parkinson-White preexcitation, either isolated or complicated (see Chapter 13); absence of a sinus node, as with a superior vena caval sinus venosus atrial septal defect (see Chapter 15) or left isomerism (see Chapter 3); ventricular tachycardia with the long QT syndromes13; or arrhythmogenic right ventricular dysplasia. Still other abnormalities, such as Marfan syndrome, which is the result of mutations in the gene that encodes fibrillin-1, are actually or potentially of functional significance but are not necessarily manifest at birth as gross structural malformations and, as a matter of convention, are usually not classified as congenital.14 And a handful of odd defects tend to escape inclusion, such as congenital kinking of the internal carotid artery.15
Because of the intimate interplay between congenital malformations of the heart and the fetal substrate, we now turn to the fetal circulation per se and the remarkable circulatory changes that occur at birth.4,16 In utero patterns of blood flow have been defined in fetal lambs after insertion of catheters into limb vessels,4 and in utero left and right ventricular outputs and flow distributions through the foramen ovale, ductus arteriosus, and pulmonary bed have been measured in human fetuses with high-resolution color Doppler ultrasound scan.16,17 The right and left ventricles do not function in series in the fetus as they do in the extrauterine circulation. Gas exchange occurs in the placenta, not in the lungs. About two thirds of the right ventricular output is diverted away from the lungs through a widely patent ductus arteriosus into the descending thoracic aorta, from which a large portion enters the umbilical circulation for oxygenation in the placenta. Pulmonary blood flow is low but meets nutritional requirements for growth of the lungs. Inferior vena cava blood, which is a composite from the umbilical vein, the left and right hepatic veins, the ductus venosus, and the distal inferior vena cava, streams in the direction of the foramen ovale into the left atrium and then into the left ventricle, assisted by the eustachian valve. About 60% of the umbilical venous return that is oxygenated in the placenta bypasses the liver through the ductus venosus and enters the inferior vena cava and right atrium. Blood from the superior vena cava is deflected within the right atrium toward the tricuspid valve, across which it reaches the right ventricle. About 70% of the relatively oxygen-rich blood ejected from the left ventricle is distributed to the coronary circulation (and thus the myocardium), to the head and neck (and thus the brain), and to the forelimbs. Almost 90% of the relatively oxygen-poor blood ejected by the right ventricle passes through the ductus arteriosus into the descending aorta to be oxygenated in the placenta. Accordingly, the fetal circulation is designed so that blood with higher oxygen saturation preferentially reaches the myocardium and brain and less saturated blood preferentially reaches the placenta.
The profound circulatory changes at birth occur almost simultaneously. The umbilical/placental circulation is eliminated, the lungs expand, rhythmic ventilation commences, oxygen tension rises as alveolar fluid is eliminated and ambient air is breathed, pulmonary vascular resistance falls, and pulmonary blood flow increases eight to 10 fold. Venous return to the left atrium increases, left atrial pressure rises, the valve of the foramen ovale closes, and the ductus arteriosus functionally closes (constricts) within hours after birth, effectively separating the pulmonary and systemic circulations.4
A number of important delayed events complete the transition from the fetal to the maturing circulation after birth. During the course of gestation, pulmonary vascular resistance falls progressively as new resistance arterioles develop. Regulation of the perinatal pulmonary circulation reflects a complex interplay between vasoconstrictor and vasodilator factors, but the net effect is a dramatic increase in pulmonary blood flow initiated by expansion of the lungs and rhythmic ventilation that reflects a shift from active pulmonary vasoconstriction in the fetus to active vasodilation in the neonate.4 Failure of this shift to occur results in persistent fetal circulation of the newborn. Thick-walled fetal pulmonary arterioles are designed to meet the full force of systemic right ventricular pressure the instant the lungs expand. As respiration commences, a marked increase in alveolar and systemic arterial oxygen tension occurs, to which pulmonary arterioles are exquisitely sensitive, setting the stage for dilation and involution. Large pulmonary arteries also play a role, although much lesser, in determination of the total drop in pressure across the lungs.
