Abstract
Transposition of the great arteries (d-TGA) occurs in 3 per 10,000 live births and makes up 5% to 7% of all congenital heart disease. Without surgery, less than 10% of individuals with d-TGA will survive the first year. Preoperative management includes prostaglandin infusion to maintain or reopen the arterial duct and balloon atrial septostomy for persistent cyanosis. The arterial switch operation (ASO) relieves cyanosis and places the left ventricle (LV) in the systemic position. For the d-TGA and intact ventricular septum, ASO is performed within the first week of life. d-TGA can occur with a large ventricular septal defect, left ventricular outflow tract obstruction, or arch hypoplasia with coarctation, and these additional lesions will impact the timing and type of surgery. Coronary artery transfer remains the most challenging part of the ASO. The presence of a single coronary artery and the presence of an intramural coronary artery are both associated with increased risk. Postoperative management typically includes use of inotropes and afterload reduction to increase cardiac output while tolerating a modest reduction in systolic blood pressure. Late presentation of d-TGA places patients at increased risk for an ASO because of deconditioning of the LV. The ASO has been performed successfully in patients outside the newborn period with a slight increase in mortality and increased need for mechanical circulatory support. For older patients, preparation of the LV with pulmonary artery banding followed by ASO or an atrial-level switch may be considered. Long-term survival and quality of life are excellent after the ASO.
Key Words
Transposition of the great arteries, arterial switch operation, cyanotic congenital heart disease, balloon atrial septostomy, postoperative management, afterload reduction, Rastelli procedure, Nikaidoh procedure
Transposition of the great arteries (TGA) makes up 5% to 7% of all congenital heart disease. It occurs in 3 per 10,000 live births. Without surgery, TGA is fatal, with a mortality rate of 30% in the first week and 90% within the first year of life. Severity of illness varies depending on anatomy, degree of mixing at the atrial and ventricular levels, and presence of systemic ventricular outflow tract obstruction, with some infants requiring emergent balloon atrial septostomy (BAS) and/or extracorporeal membrane oxygenation (ECMO) immediately after birth.
Embryology and Genetics
There are two prominent theories regarding the development of TGA. The original theory, proposed by Goor and Edwards and supported by Anderson and colleagues, is known as the “conal development hypothesis.” Per Goor and colleagues, normal absorption of the bulboventricular ledge allows the aorta to rotate to the left during normal development of the heart and become oriented over the left (or primitive) ventricle. If this absorption does not occur, there is persistence of a subaortic conus, underdevelopment of the subpulmonary conus, and dextroposition of the aorta occurs.
A second theory by del la Cruz and colleagues proposes that TGA is the result of linear, as opposed to normal, spiraling of the aortopulmonary septum. This results in the fourth aortic arch remaining in contact with the anterior conus, in alignment with the right ventricle (RV).
Animal studies have linked nodal signaling pathway genes to TGA, with ZIC3 being associated with X-linked heterotaxy and familial d-TGA. Additionally, genes CFC1, FOXH1, and PROSIT240 have been associated with isolated and syndromic d-TGA.
Anatomic Features
Mathew Baillie first described TGA in 1797, although the term transposition was not coined until 1814 by Farre. TGA describes any heart in which there is ventriculoarterial (VA) discordance. In simple terms the morphologic RV is primarily connected to the aorta, whereas the morphologic left ventricle (LV) is connected to the pulmonary artery (PA). TGA can be further subdivided based on if the morphologic right and left atria are connected to the morphologic right and left ventricles. When the atria are connected to the appropriate ventricles, they are said to have atrioventricular (AV) concordance. The atrium and ventricles usually have normal configuration, and the conduction system is also usually normal.
In simple transposition the atria are connected to the correct ventricles (AV concordance), but the RV is connected to the aorta, and the LV is connected to the main PA (VA discordance). Isolated VA discordance occurs in 50% of cases. Congenitally corrected transposition refers to both AV and VA discordance. The remainder of this chapter will focus primarily on d-TGA.
Associated Anomalies
Ventricular Septal Defects.
Ventricular septal defects (VSDs) are found in 50% patients with d-TGA. When a VSD is present, there can be malalignment of the outlet septum. Anterior displacement of the septum results in hypoplasia of the right ventricular outflow tract (RVOT) and in the case of d-TGA is associated with aortic valve hypoplasia, coarctation, hypoplastic aortic arch, and interrupted aortic arch. Posterior malalignment of the outlet septum results in LV outflow tract obstruction (LVOTO) with pulmonary valve and subpulmonary stenosis and is present in 12% to 33% of cases.
Coronary Artery Variations.
Coronary artery variations are associated with TGA, and it is imperative to know the correct anatomy before the surgery. In almost all cases the coronary arteries arise from the aortic sinuses facing, or adjacent to, the PA. Leiden convention remains the most commonly used classification system for describing coronary anatomy in TGA ( Fig. 57.1 ). Early in the experience with the arterial switch operation (ASO), atypical coronary patterns, such as a retropulmonary left coronary artery, were associated with increased risk in some series. In the current era it appears that most coronary artery patterns can undergo an ASO with acceptable risk, but the presence of a single coronary ostium or an intramural coronary artery have both been shown to contribute significantly to risk of mortality.
Pathophysiology and Clinical Presentation
In d-TGA, pulmonary and systemic circulations are acting as two closed circuits in parallel to each other. As a result, there is a higher oxygen saturation in the main PA than in the aorta. This is the basis for “transposition physiology.” Deoxygenated blood returns to the right heart and is pumped into the aorta and out to the body, while oxygen-rich blood returns from the lungs to the left heart and is pumped, once again, into the pulmonary arteries. For the patient to survive there must be adequate systemic oxygen delivery. A patent ductus arteriosus (PDA) will result in increased pulmonary blood flow, increased left atrial pressure, and increased shunting across whatever atrial septal defect (ASD) is present. A VSD will also result in some mixing, but a PDA or VSD alone may be inadequate. In a newborn the most reliable strategy to increase systemic oxygen delivery is left-to-right shunting at the atrial level, and therefore a BAS is indicated in the newborn with d-TGA and excessive cyanosis.
The rate of prenatal diagnosis of d-TGA historically has been low, but with the recommendation of obtaining an outflow tract view on fetal ultrasonography this rate has improved. Because of the low rate of prenatal diagnosis, an understanding of the clinical findings of the neonate with d-TGA is essential. Presentation varies greatly based on the degree of mixing at the ductal, atrial, and ventricular levels and if there are other anatomic lesions present, such as any degree of LVOTO. All neonates will be cyanotic to some degree, but the degree of cyanosis and hypoxemia can range from very subtle, going unnoticed until the infant fails the pulse oximetry screen in the nursery, to rapidly progressive cyanosis and hypoxemia that may become life-threatening within an hour of birth. The remainder of the physical examination may be relatively unrevealing as to the diagnosis of d-TGA. A systolic murmur, respiratory distress, and signs of heart failure may be present. The cardiac silhouette has been classically described as an “egg-on-a-string” on chest radiography, in which the heart is globular in appearance and the superior mediastinum is narrow with hyperinflated lungs and small thymus. However, chest radiography results may be normal. Electrocardiogram (ECG) findings may also be normal or show right ventricular hypertrophy depending on age of the patient. Echocardiogram should be obtained as soon as possible to make the diagnosis.
Reverse differential cyanosis higher saturations in the postductal circulation compared with the preductal circulation (right arm saturation that is lower than the lower extremities) can be seen with TGA with VSD and arch hypoplasia or interrupted arch. Reverse differential cyanosis can also occur with simple TGA when there is elevated pulmonary vascular resistance with a PDA.
Preoperative Management
Prostaglandin E 1
Most hypoxic neonates will benefit from prostaglandin E 1 (PGE 1 ). PGE 1 maintains ductal patency, increases pulmonary blood flow resulting in increased left-to-right shunting at the atrial level, and results in improved systemic oxygen saturation. PGE 1 should be initiated when d-TGA is suspected or has been diagnosed. In the setting of a closed PDA, PGE 1 may need to be started at higher doses to reopen the ductus.
PGE 1 causes systemic vasodilation, which can result in flushing of the skin and hypotension. It does have effect on the gastrointestinal system and has been associated with necrotizing enterocolitis, and long-term use has been associated with pyloric stenosis. It also penetrates the central nervous system and can cause jitteriness and seizure-like activities. One of the most common side effects in the neonatal population, especially at higher doses, is apnea. Apnea may require intubation and mechanical ventilation but has been overcome with noninvasive positive pressure with use of continuous positive airway pressure or high-flow nasal cannula. Aminophylline is effective in preventing apnea related to PGE 1 , but side effects include tachycardia, decreased cerebral blood flow, and an increased risk of necrotizing enterocolitis, and it has a narrow therapeutic window.
Balloon Atrial Septostomy
BAS, or the Rashkind procedure, is used for patients with persistent cyanosis after initiation of PGE 1 . BAS is generally viewed as a safe procedure and can be performed at the bedside under echocardiographic guidance or in the cardiac catheterization laboratory. BAS typically results in immediate improvement of mixing and arterial oxygen levels (PaO 2 and arterial oxygen saturation [SaO 2 ]). Additionally, in some cases PGE 1 can be stopped after BAS. Whether or not the procedure has been successful is determined by the clinical status of the patient and hemodynamics.
Risks of BAS include vascular injury, arrhythmia, atrial perforation, and tamponade. Recently the potential for stroke as a consequence of BAS was raised in a study by McQuillen et al., who showed increased risk of focal brain injury in neonates with TGA who underwent BAS versus those who did not. However, in a similarly powered study, Petit et al. showed no incidence of stroke in neonates who underwent BAS. Finally, in a large database review by Mukherjee et al., comparing neonates who had undergone BAS to those who had not, the infants who had undergone BAS were two times more likely to have had a stroke perioperatively. This being a retrospective chart review, one of the largest limitations to the study was timing of head imaging and inability to determine when the stroke occurred in relation to repair.
Because neonates with d-TGA and a highly restrictive ASD are at increased risk, prenatal diagnosis would identify patients at immediate need for intervention. The fetal diagnosis of an intact or restrictive atrial septum should be suspected if the atrial septum is not freely mobile and when the septum appears thick with limited or no visible shunting on color Doppler imaging with two-dimensional echocardiography. Additionally, recent studies by Divanovic et al. have demonstrated that an RAS can also be diagnosed using two-dimensional echocardiography when there is a small or absent interatrial communication and the pulmonary venous Doppler forward/reverse velocity time integral ratio is 3 or less. Punn and Silverman have also shown that a hypermobile septum with reverse diastolic PDA flow also predicts the presence of an RAS and need for urgent BAS postnatally.
It is recommended that infants with d-TGA and an intact atrial septum or RAS be delivered with a neonatologist and a cardiac specialist in the delivery with a plan for intervention and urgent transport as needed. Most centers are now recommending delivery by cesarean section in the cardiac catheterization laboratory with planned intervention at birth for infants who are expected to be hemodynamically unstable. Interventions include cardiac catheterization with BAS, possible immediate surgical intervention, and ECMO available in the catheterization laboratory if necessary. These deliveries require attendance of a neonatology team, an interventional cardiology team, a cardiologist specializing in echosonography, a cardiac intensive care specialist, and a cardiovascular surgeon with full operating team, including cardiac anesthesia and perfusion specialists.
Surgical Treatment of the Infant With Transposition of the Great Arteries
The Arterial Switch Operation
Timing of Surgery.
The ASO will restore the LV as the systemic ventricle, and it is essential that the LV be prepared for systemic work. In the fetus, both ventricles do systemic work and therefore are equally prepared for systemic work at birth. In the preoperative neonate with d-TGA and an intact ventricular septum the LV will become deconditioned as the pulmonary vascular resistance drops and LV-generated pressure decreases. Therefore to ensure that the LV is adequately prepared, the arterial switch should be performed before the LV becomes deconditioned, within the first 3 weeks of life. Furthermore, repair by 6 days of age for the uncomplicated patient with d-TGA and intact ventricular septum has been shown to be associated with decreased hospital charges and was not associated with increased mortality or worse outcome. For individuals with a nonrestrictive VSD and without obstruction to pulmonary or systemic blood flow, surgery can be safely delayed up to 90 days of age. For patients with ductal dependent systemic or PA blood flow, neonatal intervention is required.
The ASO is performed through a median sternotomy incision. The most commonly encountered anatomy of TGA is that with the great vessels oriented anterior-posterior, and the most common coronary pattern has the left anterior descending coronary and the circumflex arising from the left-facing sinus and the right coronary artery arising from the right-facing sinus ( Fig. 57.2 ). Before cannulation for cardiopulmonary bypass the aorta is separated from the main PA, and the branch pulmonary arteries are mobilized to their first branches. Marking sutures are placed in the pulmonary root at the anticipated implantation sites for the coronary arteries. The arterial cannula is placed in the distal ascending aorta near the origin of the innominate artery. Placing the aortic cannula as far cephalad as possible provides the greatest exposure of the base of the heart. Typically, both cava are separately cannulated. With commencement of cardiopulmonary bypass the ductus arteriosus is ligated proximally and distally and then divided. A vent is placed into the LV, and an antegrade cardioplegia cannula is placed in the ascending aorta. The aorta is cross-clamped, and cardioplegia is delivered via the aortic root for initial arrest, after which the ASD and/or VSD are repaired through a right atriotomy.
Coronary Transfer Techniques
The aorta is transected 2 to 3 mm cephalad to the sinotubular junction ( Fig. 57.3 ). The coronary ostia are examined and excised with a button of adjacent sinus aorta. For an adequate button to be obtained, the aortic wall is incised close to the leaflet attachment of the aortic valve. The proximal coronary arteries are mobilized to allow transfer of the coronary buttons to the pulmonary root.
Medially based trapdoor incisions are created at the sites identified by the marking sutures ( Fig. 57.4A and B ). The marking sutures help ensure proper alignment of the reimplanted coronary arteries. The trapdoor incisions minimize the rotation of the proximal coronary arteries. The coronary buttons are sewn in place using 7-0 or 8-0 polypropylene sutures. It should be noted that the reimplanted coronary ostia will occupy a more cephalad position, with respect to the neoaortic valve, than they occupied in the native aorta. Furthermore, in cases in which the proximal coronary artery has a redundant course, the coronary button may be placed even more cephalad than shown to prevent kinking of the proximal coronary artery. In situations in which the implantation site is close to the facing commissure of the pulmonary root, an oblique incision can be used rather than a medially based trapdoor incision ( Fig. 57.5 ).
When both coronary arteries arise from a single sinus of Valsalva, an intramural course of the proximal coronary artery is nearly always present ( Fig. 57.6A ). The intramural coronary will exit the aorta as though it were arising from the correct sinus of Valsalva. When the button is excised, the external course of the intramural coronary must be identified, and likely the button will include a large portion of the sinus aorta from which the coronary would normally arise. To obtain an adequate cuff of sinus aorta, separating the commissure of the aortic valve from the aortic wall may be necessary. An intramural coronary will typically have a slit-like ostium. Cutting back the origin and unroofing the common wall between the aorta and the coronary artery enlarges the ostium of the intramural coronary (see Fig. 57.6B ). It is usually possible to separate the two ostia and implant them individually (see Fig. 57.6C ). Enlargement of the slit-like ostium and unroofing can be challenging in a small neonate, and rotating the button through the vertical axis may result in a kink or buckle of the coronary. To prevent proximal coronary obstruction, it may be preferable to transfer the coronary button by rotating it in the horizontal plane (see Fig. 57.6D ). A hood of autologous pericardium or pulmonary homograft patch is used (see Fig. 57.6E ).
The closed technique is useful when a single coronary is encountered or the great vessels lie side by side and the right posterior sinus gives rise to the right and circumflex coronary arteries ( Fig. 57.7A ). The coronary button is excised as in the open technique. The PA is divided, and the superior extent of the commissures of the PA are marked externally with a suture. The Lecompte maneuver is performed, then the distal ascending aorta is anastomosed to the proximal pulmonary root (see Fig. 57.7B ). The marking suture helps prevent injury to the pulmonary valve during subsequent coronary artery reimplantation. The root is then distended with cardioplegia or by unclamping the aorta. The appropriate site for implantation of the coronary artery is then determined by positioning the coronary button over the distended root (see Fig. 57.7C ). The optimal site should allow reimplantation without kinking of either branch of the coronary artery. Often some rotation of the button is required (see Fig. 57.7D ). The coronary artery button is implanted with fine polypropylene suture.
