D-Transposition of the Great Arteries

Morphology and embryology

Complete transposition of the great arteries is one of the most common types of cyanotic congenital heart disease, and is defined as a concordant connection at the atrioventricular level and a discordant one at the ventriculoarterial level. The term "complete" was traditionally used to differentiate transposition of the great arteries from double outlet right ventricle, the latter being regarded as an incomplete form of transposition of former. The atria in transposition of the great arteries can be virtually normal, or have any type of interatrial communication. The atrioventricular junction is also relatively normal, as are the course and disposition of the conduction tissues[387]. The pulmonary trunk is in fibrous continuity with the atrioventricular valves, although they may not be wedged in between the atrioventricular valves as much as the aortic valve in concordant ventriculoarterial connection. With very few exceptions and some subtleties, the ventricular morphology is normal.

The anatomy of the coronary arteries[387], which was previously of academic interest only, has gained new importance due to the arterial switch operation. When considering the coronary arteries, it is necessary to take into account separately their origin from the aortic sinuses, their course relative to the pedicles of the arterial trunks, and the origin and course of the artery to the sinus node. The epicardial course of the arteries within the ventricular mass is virtually normal, with the left anterior descending coronary artery within the anterior interventricular groove and the right and circumflex arteries within their respective atrioventricular grooves. The origin of the coronary arteries are virtually always from the two sinuses facing the pulmonary trunk, named the right and left facing sinuses when observed from the non-facing coronary sinus[386]. Any of the three coronary arteries may arise from either of the two facing sinuses. Most (~60%) cases of transposition of the great arteries have normal coronary arterial anatomy, in which the left anterior descending and left circumflex coronary arteries branch from the left main coronary artery which arises from the right facing sinus, while the right coronary artery arises from the left facing sinus. The most common variation (~15%) is for the left circumflex coronary artery and right coronary artery to arise from the left facing sinus, the left circumflex coronary artery then running behind the pulmonary artery and through the transverse sinus, while the left anterior descending coronary artery arises normally from the right facing sinus. Almost any combination is possible, although particularly important variations are those in which one of the coronary arteries crosses in front of the subaortic infundibulum after originating from the sinus, and those in which an artery, or a common stem, runs between the aorta and the pulmonary trunk. Experience has shown that almost any pattern of coronary anatomy can be transferred successfully, although it is more difficult to avoid distortion if all the coronary arteries arise from a single sinus by one, two or three orifices.

The course of the coronary artery to the sinus node is also of importance in order to decrease the incidence of postoperative rhythm disturbances. The usual course of the artery is through the interatrial groove, having originated from the proximal part of either the right coronary artery or left circumflex coronary artery. It can also burrow deeply through the atrial wall as it ascends, placing it at risk should procedures be carried out on the superior rim of the fossa ovalis. In a small proportion of cases, perhaps 10%, the artery may cross the lateral wall of the right atrial appendage or the dome of the left atrium, and be at risk during atriotomy or Blalock-Hanlon septectomy.

Associated malformations

The most commonly associated malformations are those of the ventricular septum and of the left ventricular outflow tract. The term "simple transposition" is used to differentiate between transposition of the great arteries with coexistent atrial septal defect, ventricular septal defect, patent arterial duct, or pulmonary stenosis, from transposition of the great arteries with more complicated anomalies such as common, straddling, stenotic, or atretic atrioventricular valves, or hypoplasia or absence of ventricular chambers, the latter cases of which are referred to either by the dominant lesion, as in, for example, tricuspid atresia with discordant atrioventricular connection, or simply as complex transposition.

Ventricular septal defect. An intraventricular communication can exist at any of the basic sites expected for hearts with concordant ventriculoarterial connections. Thus the defect can be perimembranous, (that is, it abuts directly on an area of the fibrous trigone, which in this case is adjoined by the tricuspid, mitral and usually pulmonary valve), it can have exclusive muscular borders, or rarely, may be subarterial. The location of the ventricular septal defect in transposition of the great arteries is dependent on the alignment of the ventricular septum. Approximately 79% of hearts with transposition of the great arteries have a normally aligned ventricular septum, 18% have anterior alignment, and 3% have posterior malalignment. In hearts with a normally aligned ventricular septum, approximately half of the ventricular septal defects are perimembranous and half are trabecular, while in hearts with a malaligned ventricular septum approximately 75% of the resultant subpulmonary ventricular septal defect are perimembranous, the remainder being trabecular[282].

Left ventricular outflow tract obstruction. Approximately 20% of (older) infants with transposition of the great arteries with intact ventricular septum have left ventricular outflow tract obstruction. The majority of these obstructions are dynamic, and may be due to leftward septal deviation from elevated right ventricle pressures ± an elevated Qp:Qs. This type of dynamic left ventricular outflow tract obstruction often gets worse after balloon atrial septostomy as better interatrial mixing is produced, and is reliably relieved by the arterial switch operation, although some patients may develop septal hypertrophy and persistent left ventricular outflow tract obstruction following the arterial switch operation. Less commonly, left ventricular outflow tract obstruction is due to a discrete fibrous diaphragm below the pulmonary valve cusps, fibrous tissue tags arising from mitral valve apparatus or membranous septum, or from valvar pulmonary stenosis. Approximately 20% of patients with transposition of the great arteries and ventricular septal defect have left ventricular outflow tract obstruction. The obstruction is usually more severe than in patients with transposition of the great arteries with intact ventricular septum, and is thought to be due to posterior malalignment of the outlet septum, which leads to a long-segment, tunnel-like obstruction.

Almost any other cardiac lesion can coexist with transposition of the great arteries. Among the more important and common are coarctation of the aorta, which is commonly associated with a restrictive subaortic obstruction, and straddling and overriding of either of the atrioventricular valves.

Hemodynamics

In transposition of the great arteries the pulmonary artery and systemic circulations are arranged in parallel rather than in series, with the aorta arising from the right ventricle and the pulmonary artery from the left ventricle. Survival depends upon mixing between the two circulations, which can occur at the atrial level through a patent foramen ovale, atrial septal defect, or following balloon atrial septostomy, at the ventricular level through a perimembranous, muscular or malalignment ventricular septal defect (if one is present), at the great arterial level through a patent arterial duct, or through bronchial collateral vessels.

In transposition of the great arteries with intact ventricular septum mixing initially occurs through the foramen ovale and arterial duct. As pulmonary vascular resistance declines in the postnatal period, aortic to pulmonary artery shunting at the arterial duct level greatly increases, resulting in increased pulmonary blood flow and return to the left atrium. Because of the parallel circulations, the degree of shunting at the arterial level must be matched by an equal amount of left to right atrial shunting. As the arterial duct constricts and eventually closes over the first few days of life, there is less aortic to pulmonary artery shunting, and arterial hypoxemia increases. Mixing is then solely dependent on bi-directional mixing at the atrial level. However, as less pulmonary blood flow results in lower left atrium pressure, the patent foramen ovale becomes restrictive and profound hypoxemia results. Effective palliation is predicated upon maintenance of an adequate atrial-level shunt, which suffices in almost all cases, but if not, also upon the maintenance of ductal patency.

In transposition of the great arteries with a nonrestrictive ventricular septal defect or patent arterial duct, profound hypoxemia is uncommon in the neonatal period. In the presence of a nonrestrictive ventricular septal defect, there is bi-directional shunting at the ventricular level, which becomes increasingly left to right as pulmonary vascular resistance drops. The increased pulmonary blood flow results in increased return to the left atrium and left ventricle, facilitating intracardiac mixing at both ventricular and atrial levels (the latter if an adequate patent foramen ovale exists). In the presence of a large patent arterial duct and an intact septum, the degree of right to left shunting that occurs at the arterial level must be matched by an equal amount of left to right atrial shunting. Usually the left atrium is quite compliant, the patent foramen ovale adequate, and there is almost exclusive left to right atrial shunting. Due to the increased pulmonary blood flow, patients with a either a nonrestrictive ventricular septal defect or large patent arterial duct have a relatively high SaO2, usually in the 75 - 85% range. The marked volume overload, however, eventually leads to congestive cardiac failure, which is the usual presenting symptom in these patients, or if prolonged, the development of pulmonary vascular obstructive disease.

In transposition of the great arteries with a ventricular septal defect and pulmonary stenosis or pulmonary atresia the level of hypoxemia depends upon the degree of obstruction to pulmonary blood flow, and the amount of pulmonary blood flow derived from collateral vessels. The hemodynamics in infants with minimal pulmonary stenosis resemble those with a large ventricular septal defect, while those with severe stenosis or pulmonary atresia present with a clinical picture similar to other infants with diminished pulmonary blood flow and hemodynamically may be indistinguishable from patients with tetralogy of Fallot.

Clinical presentation & management

The clinical picture of infants with transposition of the great arteries ranges from extreme cyanosis without congestive failure to minimal cyanosis with profound congestive failure and circulatory collapse, depending upon the degree of mixing between the systemic and pulmonary circulations and the presence or absence of associated malformations. Infants with transposition of the great arteries and intact ventricular septum almost invariably present with cyanosis during the first week of life. Otherwise healthy newborns with cyanosis should be considered an emergency, since complete closure of the arterial duct leading to hemodynamic collapse may occur rapidly. Neonates with transposition of the great arteries and ventricular septal defect more commonly present later on in the first month of life with signs of congestive failure. Classically, these infants have difficulty feeding and subsequent failure to thrive, along with tachypnea and excessive perspiration, especially with feeding. Infants with transposition of the great arteries, ventricular septal defect and pulmonary stenosis present variably depending on the degree of pulmonary stenosis. If the pulmonary stenosis is severe, pulmonary blood flow is restrictive, hypoxemia profound, and the infant presents in the first week of life. If the pulmonary stenosis is only mild, then pulmonary blood flow may be excessive and infants present with congestive failure somewhat later in life.

The chest film in transposition of the great arteries and intact ventricular septum is frequently characteristic, but may be normal. Typically the superior mediastinum is narrow due to the anterior-posterior relationship of the great vessels and due to reduced thymic tissue. Cardiac size is initially normal but soon enlarges with the cardiac apex shifted to the left and inferiorly, giving the typical oval-shaped or egg-on-side pattern. In patients with a transposition of the great arteries and ventricular septal defect there is almost invariably increased pulmonary vascular markings. In those with transposition of the great arteries, ventricular septal defect and pulmonary stenosis, the size of the heart and the degree of pulmonary vascular markings depends upon the degree of right ventricular outflow tract obstruction and pulmonary blood flow. Patients with severe obstruction may have a normal cardiac size with decreased pulmonary markings, whereas those with only mild right ventricular outflow tract obstruction may have an enlarged cardiac silhouette and increased vascular markings.

Cardiac echocardiography is a sensitive and specific tool in the diagnosis and evaluation of an infant with transposition of the great arteries and has supplemented, and in may cases replaced, other diagnostic modalities, including cardiac cineangiography. The goals of echocardiography are

  • to define the ventriculoarterial connections and coronary arteries,
  • to assess for the presence of atrial-, ventricular-, and great arterial-level shunts,
  • to define the adequacy of intra-atrial communication,
  • to assess the subpulmonary area, with particular emphasis on defining any dynamic obstruction in transposition with an intact ventricular septum, and
  • to assess for the presence of long-tunnel stenosis occasionally present in transposition with ventricular septal defect.

Selective angiocardiograms in the right and left ventricles and frequently in the great vessels are important to the understanding of the ventriculoarterial connections, atrioventricular and semilunar valves, and associated lesions, including defects of the ventricular septum, right or left ventricular outflow obstruction, and coarctation of the aorta.

D-Transposition With Ventricular Septal Defect

In the majority of patients with D-transposition of the great arteries, as in those with normally related great arteries, perimembranous, malalignment, atrioventricular, and midmuscular ventricular septal defects are exposed through the right atrium. Techniques for closure of ventricular septal defects are discussed in the section of ventricular septal defects. Some of the perimembranous or malalignment defects can also be closed through the anterior semilunar valve; for some malalignment ventricular septal defects coexisting with multiple muscular defects, a combined transatrial and trans-neoaortic approach may be necessary. A right ventriculotomy is only very rarely indicated in closure of a ventricular septal defect, those with infundibular or subarterial ventricular septal defects or those with anterior muscular defects. A right ventricular incision may also be necessary in patients with right ventricular infundibular hypoplasia and a ventricular septal defect (often associated with hypoplasia or interruption of the aortic arch). Apical muscular defects are closed with a left ventriculotomy, or preferably, in the catheterization laboratory with a clamshell device, followed within hours by an arterial switch operation and closure of any additional ventricular septal defects. Alternatively, a clamshell device can be positioned under direct vision in the operating room. Excellent visualization of the seating of the device is obtained when both great arteries have been divided.

In approximately 10% of patients the sternum is not closed primarily; instead, the sternotomy is covered with a Silastic sheet without reapproximation of the bone edges, followed by secondary closure after surgery. Most of these patients will have had significant myocardial edema, often following intraoperative revision of the coronary anastomosis or closure of a residual ventricular septal defect and prolonged cardiopulmonary bypass.

Techniques for simultaneous repair of other associated defects (e.g., coarctation, interrupted aortic arch, and hypoplastic aortic arch) in conjunction with the arterial switch operation are discussed in sections dealing with those lesions. Patients with D-transposition of the great arteries and hypoplasia or coarctation of the aortic arch have a strong likelihood of having subvalvar obstruction of the right ventricular outflow tract. This obstruction may not be apparent preoperatively with an open ventricular septal defect and a patent arterial duct when less than full cardiac output is crossing the right ventricular outflow tract, but it may result in right ventricular hypertension and obstruction after repair. Liberal use of a patch on the right ventricular outflow tract is recommended in these cases. In the occasional case in which D-transposition of the great arteries with a ventricular septal defect is accompanied by extreme diffuse aortic hypoplasia, including the aortic valve, a Damus-Kaye-Stansel approach may be required.

Why the arterial switch operation is preferred

Primarily, there is increasing concern about late results of the atrial or physiologic type of repair: Although the hospital mortality rate for both the Mustard and the Senning operations is low, the long-term outcome of these procedures is affected by a number of late complications, the most important being a high incidence of atrial dysrhythmias (more than 50% within 10 years) and a less clearly established incidence of late right ventricular (systemic ventricular) dysfunction (approximately 10%). A variety of theoretical considerations support the assumption that the left ventricle is more suitable than the right to serve the systemic circulation. The left ventricle (with its cylindric shape, its concentric contraction pattern, and both the inlet and the outlet orifices situated in close proximity) seems ideally adapted to work as a pressure pump, whereas the right ventricle (with its crescent-shaped cavity, its large internal surface area-to-volume ratio, its bellows-like contraction pattern, and its more separated inlet and outlet segments) seems better suited to serve as a low-pressure-volume pumping chamber. Also, the left ventricle has two coronary arteries (left anterior descending and left circumflex), while the right ventricle has one (right coronary). Developmentally, the stratum compactum of the myocardium is thicker in the left ventricle than in the right, and phylogenetically, the left ventricular sinus is derived from the primitive ventricle at the stage of ventricular looping (the "original pump" of our phylum Chordata), while the conus and much of the right ventricle are derived from the bulbus cordis. Furthermore, the papillary muscles of the right ventricle are small and numerous, originating both from the septum and from the right ventricular free wall, in contrast to the two papillary muscles of the left ventricle. This architecture allows the tricuspid valve to be pulled apart as the right ventricle dilates, leading to tricuspid regurgitation. The arterial switch operation recruits the left ventricle as a systemic pump, and because atrial manipulation is essentially limited to closure of an atrial communication, it is also anticipated that after the arterial switch, atrial dysrhythmias should be significantly reduced.

For D-transposition of the great arteries with an intact ventricular septum the arterial switch operation is the procedure of choice and is carried out during the neonatal period when the left ventricle is still "prepared" to support the systemic circulation by the intrauterine physiology. Ideally, the repair should be performed within the first weeks of life. Later, there is increasing likelihood that the left ventricle will be unable to accommodate the increased workload. A number of circumstances can arise that cause postponement of surgery beyond the "safe" period for an arterial switch. For example, a neonate may be seriously ill with necrotizing enterocolitis, renal or hepatic failure, or a hemorrhage in the central nervous system. Also, the neonate may be geographically distant from a center offering the arterial switch operation, or occasionally a patient with D-transposition of the great arteries and a ventricular septal defect awaiting "elective" repair may experience spontaneous partial closure of the ventricular septal defect, resulting in a low left ventricular pressure.

Because of these possibilities, some empiric criteria for predicting postoperative left ventricular performance have been developed. Before the age of 2 weeks, every patient with D-transposition of the great arteries and an intact ventricular septum is repaired, regardless of preoperative left ventricular pressure measurements. Laboratory studies in rats have demonstrated surprisingly rapid induction (within 48 hours) of the genes responsible for the isozyme adaptation of the myocardial myosin, actin, and tropomyosin in response to an acute pressure load. Furthermore, various proto-oncogenes involved in the regulation of cell growth accumulate in rat cardiac cells within 1 hour of an acute pressure load. Stress protein HSP70 is also seen at high levels within 2 to 3 hours of an acute pressure load. Coincident to these developments has been further refinement of echocardiographic techniques to assess left ventricular mass and volume more accurately. Therefore, a successful arterial switch operation can be performed 7 to 10 days after preliminary pulmonary artery banding and placement of a modified Blalock-Taussig shunt.

In patients who have D-transposition of the great arteries with a ventricular septal defect, repair is recommend shortly after the diagnosis is made. Although the left ventricle remains "prepared" when a large septal defect maintains systemic left ventricular pressure, a delay in surgery may result in pulmonary vascular obstructive disease, failure to thrive, or pulmonary infections, and, in some cases partial closure of the ventricular septal defect results in an "unprepared" left ventricle. There is therefore no advantage in delaying corrective surgery. Palliative pulmonary artery banding is indicated only in patients with multiple muscular defects, to allow time for growth and spontaneous closure of the less surgically accessible ventricular septal defects. Also, trans-catheter closure of the muscular ventricular septal defects (avoiding a ventriculotomy) can currently be accomplished when infants reach a weight of 5 kg.

Reoperations after Mustard and Senning Operations.

Senning introduced the physiological repair transposition of the great arteries in 1958 and Mustard published his experience with the atrial switch in 1964. The Mustard operation soon became the operation of choice, and survival rates of over 90% were reported. The original Mustard operation was a two-stage correction and included a Blalock-Hanlon atrial septectomy followed by an atrial switch operation in the second or third year of life. Balloon atrial septostomy was introduced by Rashkind and Miller in 1966, considerably improving the survival of infants with transposition of the great arteries, and led to early balloon atrial septostomy followed by a Mustard operation in the first year of life as the preferred operative management. Brom and Quagebeur reintroduced the Senning operation in 1975 and thereafter it became the procedure of choice. Both operations offer excellent early, but only good mid-term results, and as such, only a few centers are currently performing the atrial switch operation as first-line therapy for transposition of the great arteries[218]. The Mustard operation consists of an atrial septectomy and placement of a baffle that directs caval blood to the mitral valve, thereby leaving the pulmonary veins to drain into the tricuspid valve. The Senning operation utilized a flap the atrial septum as the inferior wall of the caval tunnel, and a flap of lateral atrial wall as the superior wall of the caval tunnel in order to achieve the same goal. A not insignificant number of patients who are 2 - 3 decades out of the atrial switch operation are returning for management of complications associated with these operations.

Complications following atrial switch operations which may require operative therapy include systemic or pulmonary venous obstruction, baffle leaks, tricuspid valve incompetence, and right ventricular dysfunction. Complications such as residual or recurrent ventricular septal defect or left ventricular outflow tract obstruction are treated as in isolated ventricular septal defect or left ventricular outflow tract obstruction. Other complications in which operative therapy has not been completely defined include left ventricular dysfunction and arrhythmias. These complications are generally diagnosed by echocardiography, and confirmed by cardiac catheterization.

Systemic venous obstruction much more commonly follows the Mustard operation as compared to the Senning operation, affects the superior vena cava much more commonly than the inferior vena cava, and is thought to be primarily related to the shape of the baffle used in the Mustard operation. superior vena cava obstruction may be clinical silent, or can be associated with facial edema, pleural effusions, chylothorax, venous collateral on the chest wall, increased head circumference, or delayed closure of the fontanelles[379]. inferior vena cava obstruction is associated with hepatomegaly, protein losing enteropathy, ascites or leg edema. Asymptomatic isolated superior vena cava obstruction may not need treatment, however, all inferior vena cava obstructions and symptomatic superior vena cava obstructions require either balloon dilatation or operative revision.

Pulmonary venous obstruction is rare after the Senning operation and infrequent following the Mustard operation, but is a serious complication which requires prompt attention. Tachypnea, dyspnea, cough, fatigue and decreasing exercise tolerance are the common symptoms. Mild cyanosis may be present and pulmonary venous congestion or interstitial pulmonary edema may be seen on the chest film. Urgent reoperation is generally indicated, although interventional balloon dilatation has been attempted successfully.

Significant Baffle leaks are unusual, although small baffle leaks can be found in approximately 20% of studied patients following the Mustard operation, and only infrequently following the Senning operation. Indications for repair are similar to those for atrial septal defect with a left-to-right shunt. If there is a coexisting inferior vena cava or superior vena cava obstruction, a baffle leak above the site of the obstruction may cause considerable right-to-left shunting, and is repaired at the time of the relief of the venous obstruction.

Tricuspid regurgitation is more commonly seen in patients after repair of transposition of the great arteries/ventricular septal defect and may be due to morphologic abnormalities of the tricuspid valve, damage to the valve at the time of repair, or to right ventricle failure and/or arrhythmias. Symptoms include progressive exertional dyspnea, a cough and fatigue, and the chest film often shows cardiomegaly. Mild to moderate tricuspid regurgitation is usually well tolerated. Severe tricuspid regurgitation may be treated by tricuspid repair or replacement, but requires an arterial switch operation or transplantation if due to severe right ventricle failure.

Right ventricular failure not uncommonly follows atrial switch operations, and may be due to the fact that the morphological right ventricle is not capable of handling the systemic workload over many years. As in tricuspid regurgitation, right ventricle dysfunction and failure is more common in patients in whom a ventricular septal defect was repaired at the time of the atrial switch operation, and particularly in those in whom the ventricular septal defect was repaired through a right ventriculotomy. Patients who develop right ventricle failure can be treated by pulmonary artery banding followed by an arterial switch operation, or alternatively, by cardiac transplantation.

The incidence of serious arrhythmias appears to have decreased in recent years, but remains a significant source of long term morbidity and mortality. The incidence of arrhythmias appears to increase over time, the percentage of patients who remain in normal sinus rhythm being 72%, 56%, and 50% at 1, 5, and 10 years following the Mustard procedure. The more common arrhythmias include atrial fibrillation or flutter, atrioventricular dissociation, sick sinus syndrome, junctional arrhythmia, and episodes of supraventricular tachycardia. Benign arrhythmias do not require treatment. Supraventricular tachyarrhythmia is treated medically, while bradyarrhythmias may require pacemaker insertion.