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, ...