Overview: TOF is the most common cyanotic congenital heart defect. The median described incidence of TOF is 356 per 1 million live births in the United States.⁵ The classic manifestations include RVOT obstruction, ventricular septal defect (VSD), overriding of the aortic root above the VSD, and right ventricular (RV) hypertrophy (Fig. 76-1, A). These findings are a result of underdevelopment of the subpulmonary infundibulum,⁶ which is associated with anterior deviation of the conal septum. Rather than sitting between the anterior and posterior limbs of the trabecula septomarginalis (a Y-shaped bundle of muscle along the right side of the ventricular septum), the conal septum in TOF typically is fused with the anterior limb, bringing the aorta over the ventricular septum and leading to the malalignment VSD.^7,8 The septal malalignment and hypertrophy of the trabeculations of the infundibular free wall result in RVOT obstruction (Fig. 76-1, B). The VSD in TOF is located between the malaligned conal septum superiorly and the muscular septum inferiorly (i.e., a conoventricular septal defect),⁹ and it typically is large, nonrestrictive, and subaortic. For further discussion of the trabecula septomarginalis, see the section of this chapter on double-outlet RV.

The anatomic appearance of TOF varies, including TOF with pulmonary atresia and TOF with dysplastic (absent) pulmonary valve syndrome. The extent of RVOT obstruction is variable, ranging from minimal obstruction to pulmonary atresia.¹⁰ The pulmonary valve often is thickened or fused with doming leaflets and a variably hypoplastic annulus causing valvular stenosis. The size of the main and branch pulmonary arteries also varies. Patients with pulmonary valve atresia have no antegrade flow supplying the pulmonary arteries; instead, pulmonary blood flow is supplied by a patent ductus arteriosus, aortopulmonary collateral arteries, or both (e-Fig. 76-2). The central pulmonary arteries can be absent, discontinuous, or diminutive. In persons with TOF and a dysplastic pulmonary valve, congenital severe pulmonary regurgitation occurs, which often is associated with severe dilatation of the central pulmonary arteries and resultant airway compression (e-Fig. 76-3, A and B).¹¹

Etiology, Pathophysiology, and Clinical Presentation: Genetic abnormalities such as chromosome 22q11 deletion, which also leads to DiGeorge or velocardiofacial syndrome, may play an important role in some patients with this disease.¹² Many cases are sporadic, without any specific genetic abnormality identified.

Clinical manifestations are variable. Most patients have adequate pulmonary blood flow at birth, and increasing cyanosis develops early in life.¹³ If RVOT obstruction is severe, right-to-left shunting occurs, resulting in cyanosis. When the obstruction is less severe, the shunting is predominantly left-to-right (so-called pink TOF); patients with this condition can present with congestive heart failure as a result of the large VSD. Patients who have TOF with pulmonary atresia are dependent on the patent ductus arteriosus or aortopulmonary collaterals for pulmonary artery blood flow. If they are dependent on the patent ductus arteriosus, an infusion of prostaglandin E₁ is necessary to maintain ductal patency until a more stable supply of pulmonary blood flow can be established. In patients who have TOF with dysplastic pulmonary valve syndrome, presentation primarily may be with tracheobronchomalacia and air trapping, as well as cyanosis.

Other congenital heart anomalies can accompany TOF. These anomalies include right aortic arch (25%) and coronary artery anomalies such as abnormal origin of the left anterior descending (LAD) artery arising from the right coronary artery (5% to 6%) or dual LAD coronary arteries.¹⁴ When the LAD artery arises from the right, it passes over the RVOT before supplying its usual territory (e-Fig. 76-4).

Imaging: RV hypertrophy causes uplifting of the cardiac apex. Concavity is present at the location of the main pulmonary artery because of underdevelopment, causing a “wooden shoe “or “boot shape” appearance of the heart (in French, Coeur en sabot) on frontal chest radiographs, a classic sign for TOF (Fig. 76-5). The shadow of the main pulmonary artery is absent, and pulmonary vascularity is decreased.¹⁵ Rarely, dilatation of the pulmonary artery occurs as a result of an aneurysm or asymmetric pulmonary vascularity is present as a result of differential pulmonary artery stenosis and collateralization. In the absence of a thymus, the possibility of DiGeorge syndrome should be considered. A right-sided aortic arch also can be seen on the frontal chest radiograph (see Fig. 76-5).

Complete anatomic diagnosis in a neonate with TOF usually is made by echocardiography, with an infrequent need for cross-sectional imaging. CT or MRI typically is requested to determine pulmonary artery anatomy and sources of pulmonary blood flow, including the central pulmonary arteries, patent ductus arteriosus, and aortopulmonary collaterals. CT angiography is an effective modality for delineating pulmonary artery and collateral anatomy in these patients, but it has the disadvantage of using ionizing radiation.¹⁶ MRI also can accurately describe these anatomic details but without the risks of ionizing radiation. Turbo spin echo techniques can display vessels clearly, with the added advantage of demonstrating airway anatomy. The mainstay of MRI for these anatomic questions is three-dimensional, gadolinium contrast-enhanced magnetic resonance (MR) angiography, which is highly accurate compared with diagnostic catheterization.¹⁷

Treatment and Follow-up: Current management of TOF in most large centers is early single-stage reconstructive surgery, typically performed at 3 to 6 months of age.¹⁸ Staged reconstruction can be required if significant hypoplasia of the central pulmonary arteries is present; a palliative shunt is placed from the systemic to the pulmonary circulation to provide stable pulmonary blood flow. When pulmonary supply is from multiple aortopulmonary collaterals, a staged approach of unifocalization of collaterals to either a shunt or the central pulmonary arteries is utilized, eventually bringing the major vessels into continuity with the RV. VSD closure often is not tolerated until later in life in this subgroup of patients.¹⁸

The goal of surgical repair of TOF is to close the VSD and relieve the RVOT obstruction, thus providing unobstructed flow to the pulmonary vessels from the RV. The approach depends on the anatomy, including the degree of pulmonary valve annulus hypoplasia and anatomy of the pulmonary arteries. The entire repair can be performed transatrially, including VSD closure and division of muscle bundles within the RVOT to relieve obstruction, with no right ventriculotomy. If the pulmonary valve annulus is hypoplastic, a limited transannular patch may be needed to relieve the obstruction.¹⁸ This procedure inevitably results in severe pulmonary regurgitation. In the past this operation was performed with a large right ventriculotomy, which now usually is avoided. In patients who have TOF with pulmonary atresia, a limited transannular patch may be sufficient to relieve RVOT obstruction. With a longer segment atresia, an RV to pulmonary artery conduit may be required. In patients with an LAD coronary artery arising from the right coronary artery and crossing the RVOT, an RV to pulmonary artery conduit occasionally is necessary to avoid damaging the vessel (see e-Fig. 76-4).¹¹

In patients with a transannular patch, a pulmonary valve replacement may be indicated later in life to remove the volume load of pulmonary regurgitation from the RV (Video 76-1). The appropriate timing of this valve replacement is the subject of intense interest.¹⁹ In patients who require an RV to pulmonary artery conduit, a conduit replacement will be needed in time because of the somatic growth of the patient. More recently, a percutaneous pulmonary valve has become available for placement within a conduit to relieve both stenosis and regurgitation (Video 76-2).

Repaired TOF is a frequent referral diagnosis for cardiac MRI. Chronic, severe pulmonary regurgitation can lead to RV pathology. Cardiac MRI is widely considered the gold standard for assessment of RV size and function, making it particularly useful in this patient population (Video 76-3). Other questions in this patient population include anatomy of the RVOT (Video 76-4), quantification of pulmonary regurgitation (Video 76-5 and Fig. 76-6, A), assessment of branch and segmental pulmonary artery anatomy, measurement of branch pulmonary artery flow, anatomy of aortopulmonary collaterals, assessment of the left ventricle (LV), and aortic valve and root pathology.

These studies typically are performed with steady-state free-precession imaging in the vertical and horizontal long-axis planes and short axis of the ventricles, as well as parallel to the RVOT. Gadolinium-enhanced three-dimensional MR angiography offers high-resolution assessment of the distal pulmonary arteries and can evaluate for aortopulmonary collaterals. Velocity-encoded phase-contrast imaging assesses the ratio of pulmonary to systemic flow, differential pulmonary blood flow, and valve regurgitation. Delayed enhancement imaging reveals scarring or fibrosis in the heart (Fig. 76-6, B).^1,11

Use of CT for patients with repaired TOF generally is restricted to evaluation of pulmonary artery anatomy and aortic size, particularly in patients in whom MRI is contraindicated (e.g., patients with an internal defibrillator). Electrocardiographic-gated multidetector array computed tomography can provide RV size and systolic function, although with less temporal resolution than MRI.

Overview: TGA is defined by discordant ventriculoarterial relations; the aorta is connected to the RV and the pulmonary artery is connected to the LV. The most common type of TGA, defined by the segmental anatomy of the heart, is {S, D, D} transposition—that is, visceral and atrial situs solitus (S), ventricular D loop (D), and dextroposition of the aortic valve (D) (see Chapter 63). The aortic valve is side by side or anterior and rightward of the pulmonary valve (Fig. 76-7, A) and usually is separated from the tricuspid valve by conal tissue. “D-looped TGA” also is acceptable terminology.¹

{S, D, D} TGA is the second most common cyanotic congenital heart disease.¹¹ The median described incidence of {S, D, D} TGA is 303 per 1 million live births.⁵

Etiology, Pathophysiology, and Clinical Presentation: TGA usually is not associated with extracardiac anomalies or syndromes.¹⁵ It is associated with VSD in approximately 40% to 45% of cases. Other anomalies that can be seen in patients with TGA are LVOT obstruction, aortic coarctation or interrupted aortic arch, tricuspid valve abnormalities, or, less commonly, mitral valve abnormalities, leftward juxtaposition of the atrial appendages, and RV hypoplasia.²⁰

Patients present with cyanosis as a result of parallel systemic and pulmonary circulations. Deoxygenated blood returns to the right atrium via systemic veins, then passes through the RV to the aorta. Pulmonary venous blood returns to the left atrium and LV, then back to the pulmonary artery. Survival depends on communications between the systemic and pulmonary circulations, typically via an atrial septal defect, patent ductus arteriosus, and/or VSD.

Imaging: The radiographic appearance is variable. The classic finding of TGA by chest radiography is the “egg on a string” sign (Fig. 76-7, B), which is caused by a narrow mediastinum and the cardiac shadow. The narrow mediastinum is a result of stress-related thymic atrophy and the parallel position of the great vessels, with the pulmonary artery obscured by the aorta. The heart size varies from normal to enlarged.¹⁵

Cross-sectional imaging is seldom used for preoperative evaluation of TGA, but it can be helpful for specific questions that are unanswered by echocardiography, typically complex associated abnormalities of the aorta or pulmonary arteries. MRI often is preferred instead of CT to avoid the risks of ionizing radiation. In some centers, CT may be preferred because it offers greater accessibility and decreases the need for anesthesia or sedation as a result of shorter scanning times. CT scans should be performed with parameters optimized to minimize exposure of the patient to ionizing radiation.

Treatment and Follow-up: In newborn infants with {S, D, D} TGA, adequacy of the communications between the pulmonary and systemic circulations is critical. Infusion of prostaglandin E₁ maintains ductal patency. If the atrial septum is restrictive, urgent cardiac catheterization for balloon atrial septostomy often is required.²¹ In this procedure, a balloon septostomy catheter is passed across the atrial septum into the left atrium. The balloon is inflated and the catheter is sharply pulled back, fracturing the septum and enlarging the opening, allowing for greater mixing of oxygenated and deoxygenated blood.

In the early days of surgical repair of TGA, the atrial switch was used (i.e., “Mustard” or “Senning” procedures). With the atrial switch procedure, an intraatrial baffle is created with use of pericardium or native atrial tissue, which directs systemic venous return to the morphologic LV and pulmonary artery, and pulmonary venous return to the morphologic RV and aorta (Fig. 76-8, A and B).

The atrial switch has been replaced by the arterial switch operation, which has been used widely in the United States since the mid to late 1980s. In this operation the ascending aorta and pulmonary artery are transected at the sinotubular junction and anastomosed to the concordant ventricle, the aorta to the left and the pulmonary artery to the right, after the pulmonary artery is relocated anterior to the aorta (the “Lecompte maneuver”) (Fig. 76-9, A). The coronary arteries are relocated from the native aorta to the neoaorta (Fig. 76-9, B).²²