Coarctation of the aorta occurs in approximately 6% to 8% of patients with congenital heart disease. The New England Regional Infant Cardiac Program (NERICP) identified coarctation of the aorta as the fourth most common lesion requiring cardiac catheterization or surgery during the first year of life (1). Coarctation accounted for 7.5% of infants encountered in the program between 1969 and 1974. The prevalence is actually higher because the NERICP reported only infants requiring intervention during the first year of life. As with most left-sided obstructive lesions, coarctation occurs more commonly in males than in females, with a male:female ratio ranging from 1.27 to 1.74 (1,2).

A genetic influence on the development of coarctation has long been recognized in patients with Turner syndrome (45X), in whom about 35% are affected. Interestingly, recent data indicate that approximately 5% of girls presenting with coarctation also have Turner syndrome (3). The evidence of an important genetic influence on the development of left-sided obstructive lesions is clear (4,5,6,7,8,9). For example, linkage studies have identified multiple overlapping genetic loci for left-sided obstructive lesions, including coarctation, strongly supporting the notion that these lesions are causally related (7,8). NOTCH1 mutations have been identified in some patients with bicuspid aortic valve, aortic valve stenosis, coarctation, and hypoplastic left heart syndrome (9), and more recently mutations in MCTP2 have been identified in patients with coarctation as well as hypoplastic left heart syndrome (10). Environmental influence on the development of coarctation also has been suggested by a study detecting a seasonal variation, with the incidence of coarctation peaking in the late fall and winter (11).

The aortic arch and its branches develop during the sixth to eighth week of human gestation. The embryologic third aortic arches persist as the common carotid arteries. The left fourth aortic arch forms the thoracic aortic arch and isthmus and the right fourth arch normally involutes. The embryologic sixth aortic arches persist as the proximal pulmonary arteries, with the left sixth aortic arch developing distally into the ductus arteriosus. Thoracic coarctation is, therefore, a manifestation of abnormal development of the embryologic left fourth and sixth aortic arches (12). The underlying cause is not well understood, but two concepts have been advanced, neither of which is entirely satisfactory: the ductus tissue theory and the hemodynamic theory.

Coarctation typically occurs at the site of insertion of the ductus arteriosus. The ductus tissue theory proposes that coarctation develops as the result of migration of ductal smooth muscle cells into the periductal aorta, with subsequent constriction and narrowing of the aortic lumen (13). This concept is concordant with the clinical observations that coarctation often becomes manifest after ductus closure and that it may be palliated in the newborn with prostaglandin E₁ infusion. However, the ductal tissue theory does not adequately explain some instances of aortic coarctation that occur distant from the ductus insertion.

The hemodynamic theory proposes that coarctation develops because of hemodynamic disturbances that reduce the volume of blood flow through the fetal aortic arch (14). In the normal fetus
the aortic isthmus receives only 10% of the combined ventricular output, which explains the observation that the normal neonatal isthmus diameter is only about 70% to 80% of the diameter of the ascending aorta (14). According to the hemodynamic theory, intracardiac lesions that diminish the volume of left ventricular outflow promote development of coarctation in the fetus by reducing flow through the aortic isthmus. This theory does help to explain the common association of coarctation with ventricular septal defect, aortic stenosis, and hypoplasia of the transverse aortic arch. It is also consistent with fetal echocardiographic studies demonstrating that hypoplasia of the transverse arch and isthmus are common in fetuses with coarctation (15). An interesting variation of the hemodynamic theory has been proposed to explain coarctation in girls with Turner syndrome. It is suggested that fetal lymphatic obstruction, which may cause the webbed neck in Turner syndrome, also leads to distended thoracic ducts that compress the fetal aorta and promote the development of coarctation (16).

Coarctation of the aorta most commonly is a discrete stenosis in the upper thoracic aorta, at or near the insertion of the ductus arteriosus (Fig. 45.2). Most coarctations, therefore, are properly described as juxtaductal in location. The gross morphology of coarctation includes an intimal and medial malformation and a prominent posterior infolding (the posterior shelf) which often extends around the entire circumference of the aorta (17). Although coarctation is most often a discrete stenosis (Fig. 45.3), it may be long-segment and/or tortuous, and may be associated with isthmus and transverse arch hypoplasia (Fig. 45.4). Hypoplasia of the transverse aortic arch (Fig. 45.5) and isthmus proximal to the coarctation occurs often in infants, particularly those with associated left-ventricular outflow obstruction or a ventricular septal defect (18,19). Less commonly, coarctation can occur in the abdominal aorta where it may be a complex long-segment stenosis that involves the renal arteries as well (some of these cases may be the result of prior aortitis).

Histologic examination of juxtaductal coarctation reveals thick intimal and medial ridges that protrude posteriorly and laterally into the aortic lumen (Fig. 45.2). Associated intimal thickening and hyperplasia is particularly prominent in older patients (17). The ductus or ligamentum arteriosus inserts at the same level anteromedially. Intimal proliferation and disruption of elastic tissue may occur distal to the coarctation (the jet lesion), where high-velocity flow impacts the arterial wall. It is this distal site where infective endarteritis, intimal dissections, or aneurysms may occur. Cystic medial necrosis, consisting of depletion and disarray of medial elastic tissue, occurs commonly in the aorta adjacent to the coarctation site (20) and in the ascending aorta as well. In some patients, cystic medial necrosis provides the histologic substrate for late aortic aneurysm formation or dissection.

Fetal hemodynamics rarely are disturbed by the presence of a coarctation because normally only 10% of the combined ventricular output traverses the aortic isthmus in utero. After birth, however, with closure of the foramen ovale and ductus arteriosus, a substantially larger volume flow must cross the stenotic aortic segment. Therefore, important hemodynamic disturbances may occur postnatally. Depending on the severity of coarctation and the presence of associated cardiac lesions, these hemodynamic changes range from mild systolic hypertension to severe heart failure and shock.

Coarctation of the aorta increases impedance to left ventricular outflow, and elevates systolic pressure in the left ventricle, the ascending aorta, and its branches. Depending on the severity of the stenosis, the cardiac output, and the extent of the collateral circulation the systolic pressure gradient across a coarctation may be as high as 50 to 60 mm Hg at rest. In many patients, a pressure gradient is present throughout systole and diastole (Fig. 45.6). A variety of compensatory mechanisms assist the left ventricle in response to the increase in outflow impedance. Left ventricular myocardial hypertrophy is perhaps the most important. Myocardial hypertrophy tends to normalize myocardial wall stress and ventricular afterload (27) and helps maintain normal systolic ventricular function. In isolated coarctation left ventricular end-diastolic volume is relatively normal, and the end-systolic volume may be reduced. Thus, left ventricular ejection fraction is normal to increased in most children with coarctation of the aorta (in the absence of heart failure).

If a coarctation is severe or develops rapidly, as in a newborn upon ductal closure, left ventricular systolic dysfunction and heart failure may ensue. The hemodynamic consequences include diminished stroke volume, increased left ventricular end-diastolic pressure, elevated left atrial pressure, pulmonary venous congestion, and pulmonary artery hypertension. If cardiac output is severely compromised, diminished myocardial perfusion and the development of acidosis depress myocardial contractility further. This clinical scenario is particularly common in the first weeks of life. Compensatory mechanisms include activation of the sympathetic nervous system (to increase heart rate and enhance myocardial contractility) and the Frank–Starling mechanism (to increase left ventricular end-diastolic volume and help maintain a normal stroke volume). The immature myocardium, however, is relatively ineffective in using these compensatory responses (28). The neonatal myocardium lacks mature sympathetic innervation as a result, in part, of a decrease in beta-receptor density. Further, compared with the adult myocardium, the neonatal left ventricular myocardium is poorly compliant and less able to enlist the Frank–Starling mechanism to preserve stroke volume. Finally, with severe coarctation in the newborn left ventricular pressure overload occurs rapidly, upon closure of the ductus arteriosus, without time for myocardial hypertrophy to develop. Left ventricular afterload and wall stress, therefore, increase in a relatively uncompensated fashion. It is clear that many factors make the immature myocardium particularly vulnerable to the hemodynamic disturbances imposed by severe coarctation, and explain the observation that ventricular systolic dysfunction and heart failure are confined primarily to the first weeks of life.

Coarctation also may cause left ventricular diastolic dysfunction. Echocardiographic studies have demonstrated a decreased rate of early left ventricular diastolic relaxation, with consequent abnormalities in diastolic filling characterized by a shift of left ventricular filling into late diastole (29). These abnormalities in diastolic function are believed to relate to diminished left ventricular compliance caused by myocardial hypertrophy, myocardial fibrosis, and, possibly an increase in the inotropic state of the myocardium. An important functional consequence is an increase in left ventricular end-diastolic pressure at any given filling volume. Thus, left atrial hypertension and pulmonary venous congestion may occur, particularly in patients with an increased left ventricular end-diastolic volume.

An associated congenital intracardiac defect compounds the hemodynamic burden in some patients with a coarctation. Valvar or subvalvar aortic stenosis will increase the left ventricular systolic
pressure and ventricular afterload further. A large ventricular septal defect, patent ductus arteriosus, or mitral regurgitation will increase left ventricular end-diastolic volume and ventricular preload. In concert with diminished left ventricular compliance, the augmented diastolic volume leads to an increase in left ventricular end-diastolic pressure. Subsequently, left atrial pressure will rise, and pulmonary venous and arterial hypertension may develop. Therefore, heart failure and pulmonary artery hypertension are relatively common in children with coarctation and associated aortic stenosis and/or ventricular septal defect as a consequence of disturbances in left ventricular preload, afterload, and diastolic function.

Abnormalities in peripheral vascular physiology also occur in patients with coarctation. Systolic arterial hypertension is a manifestation of the coarctation stenosis, but it also reflects changes in vascular reactivity, arterial wall compliance, and baroreceptor function. Studies of patients after coarctation repair have demonstrated abnormal arterial vascular function (30,31,32), as well as resetting of the baroreceptor reflex in some patients with persistent hypertension (33). Such abnormalities in arterial physiology, which may be present after successful anatomic relief of coarctation, help to explain the occurrence of systolic hypertension in some patients many years after coarctation repair.

The clinical presentation of coarctation generally follows one of three patterns: an infant with congestive heart failure, a child with a heart murmur, or a child or adolescent with systemic arterial hypertension. When coarctation presents in infancy, it often presents as a catastrophic illness. Congestive heart failure and shock can occur suddenly as the ductus arteriosus closes. A large proportion of these infants have coarctation with important associated structural lesions such as a ventricular septal defect or aortic stenosis. In an infant with severe coarctation and a large ventricular septal defect, the sudden onset of ventricular dysfunction, low cardiac output, shock, and acidosis classically develops around 8 to 10 days of life. Multiorgan system failure, particularly renal failure and/or necrotizing enterocolitis, and death occur rapidly unless definitive medical and surgical interventions are provided rapidly.

Coarctation of the aorta may present later in childhood as systolic upper extremity hypertension or as a heart murmur. Delayed diagnosis beyond infancy is common as physical findings may be subtle, and most of these patients are asymptomatic. On careful investigation, some will report lower extremity claudication with exercise or frequent headaches. In a review of children (beyond infancy) presenting with coarctation at Columbia University between 1969 and 1978, the median age at diagnosis was 10 years. The most common causes for referral were hypertension or a heart murmur. The correct diagnosis of coarctation was made by the referring physician in only 14% of cases (34).

Patients with untreated coarctation have a poor natural history, characterized by significant morbidity and early mortality. In his classic 1970 study, Campbell reported natural history data obtained from necropsy and clinical records on 465 patients with coarctation (40). Only subjects who survived the first year of life were evaluated, excluding infants with critical coarctation. Nevertheless, Campbell’s natural history data for untreated coarctation beyond infancy documented a mean age at death of 34 years (median, 31 years), with 75% of patients having died by 46 years of age. The most common causes of death were congestive heart failure (26%), aortic rupture (21%), endocarditis (18%), and intracranial hemorrhage (12%). Given such a poor prognosis untreated, it is apparent that intervention is indicated in virtually all patients with coarctation of the aorta. The timing of therapy depends on the nature of the patient’s presentation.