Introduction: Morphology This chapter deals with one of the most complex—and difficult to treat surgically—of all congenital cardiac malformations: tetralogy of Fallot with pulmonary atresia We focus particularly on tetralogy of Fallot with pulmonary atresia (TOF/PA) and major aortopulmonary collateral arteries (MAPCAs) MAPCAs are defined as systemic arterial vessels that terminate in the lung parenchyma These vessels form during embryologic development and persist until birth and after A wide spectrum of abnormalities of the intraparenchymal, or native, pulmonary artery system, including hypoplasia and arborization deficiencies, is essentially always present with MAPCAs MAPCAs are most often associated with the cluster of defects that include TOF, PA, and absent ductus arteriosus There are very good reasons why this association is most common, as will be outlined Although this chapter deals solely with TOF/PA, it is important to appreciate that MAPCAs can be associated, albeit less often, with a wide spectrum of intracardiac anomalies, including transposition, double-outlet right ventricle, common arterial trunk, congenitally corrected transposition, PA with intact ventricular septum, other forms of single ventricle, atrioventricular septal defect, atrial isomerism, and others The common theme that links MAPCAs with all of these varied intracardiac anomalies is that there is either absence or severe restriction of all central sources of pulmonary blood flow during embryologic development; in essence, absence of a ductus arteriosus and PA There are unusual “transition” cases in which there is a nearly atretic but nevertheless patent pulmonary valve A ductus arteriosus to confluent central branch pulmonary arteries is essentially never present in association with MAPCAs, although a unilateral ductus to one native branch pulmonary artery can occur with MAPCAs supplying the contralateral lung if it has no embryologic central source of blood flow Several arguments can be marshalled to explain why TOF is the most common intracardiac anomaly associated with MAPCAs First, tetralogy is simply the most commonly occurring intracardiac anomaly relative to the other intracardiac anomalies associated with MAPCAs Second, restriction of pulmonary blood flow is an intrinsic feature of tetralogy in all its forms, whereas this is not the case with some of the other anomalies Third and most interesting, embryologic absence of the ductus arteriosus is a common occurrence in all forms of tetralogy An absent ductus occurs in about one-third of patients with tetralogy; this association appears to span the entire spectrum of severity of tetralogy, from mild pulmonary stenosis all the way to PA In simple tetralogy, absence of the ductus is usually of no clinical consequence, either during embryologic development or after birth, since forward flow across the stenotic pulmonary valve is an adequate source of central pulmonary artery blood flow In TOF/PA, however, absence of a ductus arteriosus sets up the embryologic substrate for persistence of foregut blood supply to the lungs and lack of development of native pulmonary arteries (i.e., no central source of pulmonary blood flow) It is not surprising that in newborns with TOF/PA, approximately two-thirds have a ductus arteriosus, well-developed native confluent branch pulmonary arteries, and no MAPCAs, whereas about one-third have absent ductus arteriosus, abnormal native pulmonary arteries, and MAPCAs Prevalence and Etiology Because there is no uniformity in the methods of classifying the patients to be described, it is difficult to provide precise incidence for those having TOF/PA When TOF is considered as an overall entity, the lesion makes up almost 4% of patients with congenitally malformed hearts It is likely that up to one-tenth of these will have had PA rather than pulmonary stenosis In many cases, the intracardiac anatomy suggests that the pulmonary outflow tract was initially patent but became atretic during fetal life In others, particularly those with systemic-to-pulmonary collateral arteries, the atresia was probably part of the initial developmental abnormality PA, rather than stenosis, is particularly frequent when tetralogy is found in association with deletions of chromosome 22q11 Such deletions have also been established as the cause of the velocardiofacial syndrome, which is typically found with TOF as the cardiac component of the association Morphology PA exists when there is either complete obstruction or absence of the communication normally present between the cavities of the ventricular mass and the pulmonary arteries In the setting of TOF, the obstruction can sometimes be produced by an imperforate pulmonary valve (Fig 36.1A) More often, the blockage of the pathway is muscular, either at the entrance to or at the distal end of the subpulmonary infundibulum (Fig 36.1B) The connection is lacking when there is absence of the pulmonary trunk, with the extreme form represented by absence of all the intrapericardial pulmonary arteries (Fig 36.1C) FIG 36.1 Varying arrangements at the pulmonary ventriculoarterial junction that underscore the phenotypic cardiac variants in the setting of tetralogy with pulmonary atresia There is further variability with regard to the morphology of the ventricular septal defect Just as TOF with pulmonary stenosis can be found with marked variability in intracardiac morphology, so can TOF/PA.1 Before discussing the crucial variations in pulmonary arterial anatomy, therefore, the variations in morphology within the heart are discussed in the following paragraphs Intracardiac Structure Significant variations are to be found in the morphology of the ventricular outflow tracts, the morphology of the interventricular communication, and the precise connection of the aorta to the ventricular mass as well as in the associated malformations Apart from the associated malformations, these features are interrelated To fulfil the basic diagnosis as TOF, the aorta must be connected to the ventricles in posterior position relative to the atretic pulmonary outflow tract The aortic valvar orifice overrides the crest of the muscular ventricular septum, albeit to varying degrees The phenotypic feature of tetralogy