A little over a hundred years ago, Sir William Osler, in his classic textbook The Principles and Practice of Medicine (New York, Appleton & Co, 1892, pp 659–663), devoted only five pages to “Congenital Affections of the Heart,” with the first sentence declaring, that “[t]hese [disorders] have only limited clinical interest, as in a large proportion of cases the anomaly is not compatible with life, and in others nothing can be done to remedy the defect or even to relieve symptoms.” Fortunately, in the intervening century, considerable progress has been made in understanding the basis for these disorders and their effective treatment.
The most common birth defects are cardiovascular in origin. These malformations are due to complex multifactorial genetic and environmental causes, but recognized chromosomal aberrations and mutations of single genes account for <10% of all cardiac malformations. Congenital heart disease (CHD) complicates ∼1% of all live births in the general population—about 40,000 births/year—but occurs more frequently in the offspring (about 4–5%) of women with CHD. Owing to the remarkable surgical advances over the last 60 years, >90% of afflicted neonates and children now reach adulthood; women with CHD may now frequently successfully bear children after competent repairs. As such, the population with CHD is steadily increasing. Women with aortic disease (e.g., aortic coarctation or Marfan's syndrome) risk aortic dissection. Patients with cyanotic heart disease, pulmonary hypertension, or Marfan's syndrome with a dilated aortic root generally should not become pregnant; those with correctable lesions should be counseled about the risks of pregnancy with an uncorrected malformation versus repair and later pregnancy.
More than one million adults with operated or unoperated CHD live in the United States today and, thus, outnumber the 800,000 children with CHD. Because true surgical cures are rare, and all repairs—be they palliative or corrective—may leave residua, sequelae, or complications, most require some degree of lifetime expert surveillance. The anatomic and physiologic changes in the heart and circulation due to any specific CHD lesion are not static but, rather, progress from prenatal life to adulthood. Malformations that are benign or escape detection in childhood may become clinically significant in the adult. For example, a functionally normal congenitally bicuspid aortic valve may thicken and calcify with time, resulting in significant aortic stenosis; a well-tolerated left-to-right shunt of an atrial septal defect (ASD) may result in cardiac decompensation or pulmonary hypertension only after the fourth to fifth decade.
CHD is generally the result of aberrant embryonic development of a normal structure or failure of such a structure to progress beyond an early stage of embryonic or fetal development. This brief section serves to introduce the reader to normal development so that defects may be better understood; by necessity, it is not exhaustive. Cardiogenesis is a finely tuned process with transcriptional control of a complex group of regulatory proteins that activate or inhibit their gene targets in a location- and time-dependent manner. At about three weeks of embryonic development, two cardiac cords form and become canalized; at that point, the primordial cardiac tube develops from two sources (cardiac crescent or the first heart field, pharyngeal mesoderm or the second heart field); by 21 days, these fuse into a single cardiac tube beginning at the cranial end. The cardiac tube then elongates and develops discrete constrictions with the following segments from caudal to cranial location: sinus venosus receives the umbilical, vitelline, and common cardinal veins: atrium, ventricle, bulbus cordis, truncus arteriosus, aortic sac, and the aortic arches. The cardiac tube is fixed at the sinus venosus and arterial ends.
Subsequently, in the next few weeks, differential growth of cells causes the tube to elongate and loop as an “S” with the bulboventricular portion moving rightward and the atrium and sinus venosus moving posterior to the ventricle. The primitive atrium and ventricle communicate via the atrioventricular canal from which the endocardial cushion develops into two parts (ventrally and dorsally). The cushions fuse and divide the atrioventricular canal into two atrioventricular inlets and also migrate to help form the ventricular septum. The primitive atrium is divided first by a septum primum membrane, which grows down from the superior wall to the cushions; as this fusion occurs, the mid-portion resorbs in the center forming the ostium secundum. Rightward of the septum primum, a second septum secundum membrane grows down from the ventral-cranial wall toward—but not reaching—the cushions, and covering most, but not all, of the ostium secundum, resulting in a flap of the foramen ovale. The primitive ventricle is partitioned by a finely tuned set of events. The interventricular septum grows up toward the cushions, and the cushions form an upper inlet septum; between the two portions is a hole called the interventricular foramen. The left and right ventricles begin to develop side by side, and the atria and their respective inlet valves align over their ventricles. Finally, these two parts of the septum fuse with the bulboventricular ridges, which, once having septated the truncus arteriosus, extend into the ventricle. The bulbocordis divides into a subaortic portion as the muscular conus resorbs, while the subpulmonary section has elongation of its muscular conus. Spiral division of the common truncus arteriosus rotates and aligns the pulmonary artery and aortic portions over their respective outflow tracts, the aortic valve moving posterior over the left ventricle (LV) outflow tract and the pulmonary valve moving anterior over the right ventricle (RV) outflow tract, with a wraparound relationship of the two great arteries.
Early on, the venous systems are bilateral and symmetric and enter two horns of the sinus venosus. Ultimately, except for the coronary sinus, most of the left-sided portions and the left sinus–venosus horn regress and the systemic venous system empties into the right horn via the inferior and superior vena cavae. The pulmonary venous system, initially connecting to the systemic venous system, develops as buds from the developing lungs fuse together in the pulmonary venous confluence at which point the connection to the systemic system regresses. Simultaneously, a projection from the back wall of the left atrium (the common pulmonary vein) grows posteriorly to ...