Tetralogy of Fallot
(from Kliegman Nelson Pediatric 18th Edition, Cyanotic Congenital Heart Lesions: Lesions Associated with Decreased Pulmonary Blood Flow)
Tetralogy of Fallot is one of the conotruncal family of heart lesions in which the primary defect is an anterior deviation of the infundibular septum (the muscular septum that separates the aortic and pulmonary outflows). The consequences of this deviation are (1) obstruction to right ventricular outflow (pulmonary stenosis), (2) ventricular septal defect (VSD), (3) dextroposition of the aorta with override of the ventricular septum, and (4) right ventricular hypertrophy ( Fig. 1 ). Obstruction to pulmonary arterial blood flow is usually at both the right ventricular infundibulum (subpulmonic area) and the pulmonary valve. The main pulmonary artery is often small, and various degrees of branch pulmonary artery stenosis may be present. Complete obstruction of right ventricular outflow (pulmonary atresia with VSD) is classified as an extreme form of tetralogy of Fallot . The degree of pulmonary outflow obstruction varies, with the severity of the obstruction determining the degree of the patient's cyanosis.
The pulmonary valve annulus may be of nearly normal size or quite small. The valve itself is often bicuspid and, occasionally, is the only site of stenosis. More commonly, the subpulmonic or infundibular muscle, the crista supraventricularis, is hypertrophic, which contributes to the subvalvar stenosis and results in an infundibular chamber of variable size and contour. When the right ventricular outflow tract is completely obstructed (pulmonary atresia), the anatomy of the branch pulmonary arteries is extremely variable; a main pulmonary artery segment may be in continuity with right ventricular outflow, separated by a fibrous but imperforate pulmonary valve, or the entire main pulmonary artery segment may be absent. Occasionally, the branch pulmonary arteries may be discontinuous. In these more severe cases, pulmonary blood flow may be supplied by a patent ductus arteriosus (PDA) and by multiple major aortopulmonary collateral arteries (MAPCAs) arising from the ascending and descending aorta.
The VSD is usually nonrestrictive and large, is located just below the aortic valve, and is related to the posterior and right aortic cusps. Rarely, the VSD may be in the inlet portion of the ventricular septum (atrioventricular septal defect). The normal fibrous continuity of the mitral and aortic valves is usually maintained. The aortic arch is right sided in 20% of cases, and the aortic root is usually large and overrides the VSD to a varying degree. When the aorta overrides the VSD by more than 50% and if there is muscle separating the aortic valve and the mitral annulus (subaortic conus), this defect is usually classified as a form of double-outlet right ventricle; however, the pathophysiology is the same as that of tetralogy of Fallot.
Systemic venous return to the right atrium and right ventricle is normal. When the right ventricle contracts in the presence of marked pulmonary stenosis, blood is shunted across the VSD into the aorta. Persistent arterial desaturation and cyanosis result. Pulmonary blood flow, when severely restricted by the obstruction to right ventricular outflow, may be supplemented by the bronchial collateral circulation (MAPCAs) and, in the newborn, by a PDA. Peak systolic and diastolic pressures in each ventricle are similar and at systemic level. A large pressure gradient occurs across the obstructed right ventricular outflow tract, and pulmonary arterial pressure is normal or lower than normal. The degree of right ventricular outflow obstruction determines the timing of the onset of symptoms, the severity of cyanosis, and the degree of right ventricular hypertrophy. When obstruction to right ventricular outflow is mild to moderate and a balanced shunt is present across the VSD, the patient may not be visibly cyanotic (acyanotic or “pink” tetralogy of Fallot). When obstruction is severe, cyanosis will be present from birth and worsen when the ductus begins to close.
Infants with mild degrees of right ventricular outflow obstruction may initially be seen with heart failure caused by a ventricular-level left-to-right shunt. Often, cyanosis is not present at birth, but with increasing hypertrophy of the right ventricular infundibulum and patient growth, cyanosis occurs later in the 1st yr of life. It is most prominent in the mucous membranes of the lips and mouth and in the fingernails and toenails. In infants with severe degrees of right ventricular outflow obstruction, neonatal cyanosis is noted immediately. In these infants, pulmonary blood flow may be dependent on flow through the ductus arteriosus. When the ductus begins to close in the 1st few hours or days of life, severe cyanosis and circulatory collapse may occur. Older children with long-standing cyanosis who have not undergone surgery may have dusky blue skin, gray sclerae with engorged blood vessels, and marked clubbing of the fingers and toes. Extracardiac manifestations of long-standing cyanotic congenital heart disease are described in Chapter 434 .
Dyspnea occurs on exertion. Infants and toddlers play actively for a short time and then sit or lie down. Older children may be able to walk a block or so before stopping to rest. Characteristically, children assume a squatting position for the relief of dyspnea caused by physical effort; the child is usually able to resume physical activity within a few minutes. These findings occur most often in patients with significant cyanosis at rest.
Paroxysmal hypercyanotic attacks (hypoxic, “blue,” or “tet” spells) are a particular problem during the 1st 2 yr of life. The infant becomes hyperpneic and restless, cyanosis increases, gasping respirations ensue, and syncope may follow. The spells occur most frequently in the morning on initially awakening or after episodes of vigorous crying. Temporary disappearance or a decrease in intensity of the systolic murmur is usual as flow across the right ventricular outflow tract diminishes. The spells may last from a few minutes to a few hours but are rarely fatal. Short episodes are followed by generalized weakness and sleep. Severe spells may progress to unconsciousness and, occasionally, to convulsions or hemiparesis. The onset is usually spontaneous and unpredictable. Spells are associated with reduction of an already compromised pulmonary blood flow, which, when prolonged, results in severe systemic hypoxia and metabolic acidosis. Infants who are only mildly cyanotic at rest are often more prone to the development of hypoxic spells because they have not acquired the homeostatic mechanisms to tolerate rapid lowering of arterial oxygen saturation, such as polycythemia.
Depending on the frequency and severity of hypercyanotic attacks, one or more of the following procedures should be instituted in sequence: (1) placement of the infant on the abdomen in the knee-chest position while making certain that the infant's clothing is not constrictive, (2) administration of oxygen (although increasing inspired oxygen will not reverse cyanosis caused by intracardiac shunting), and (3) injection of morphine subcutaneously in a dose not in excess of 0.2 mg/kg. Calming and holding the infant in a knee-chest position may abort progression of an early spell. Premature attempts to obtain blood samples may cause further agitation and be counterproductive.
Because metabolic acidosis develops when arterial PO2 is <40 name="4-u1.0-B978-1-4160-2450-7..50432-1--p190">intravenous administration of sodium bicarbonate is necessary if the spell is unusually severe and the child shows a lack of response to the foregoing therapy. Recovery from the spell is usually rapid once the pH has returned to normal. Repeated blood pH measurements may be necessary because rapid recurrence of acidosis may ensue. For spells that are resistant to this therapy, drugs that increase systemic vascular resistance, such as intravenous phenylephrine, can improve right ventricular outflow, decrease the right-to-left shunt, and improve the symptoms. β-Adrenergic blockade by the intravenous administration of propranolol (0.1 mg/kg given slowly to a maximum of 0.2 mg/kg) is also useful.
Growth and development may be delayed in patients with severe untreated tetralogy of Fallot, particularly when oxygen saturation is chronically <70%.>
The pulse is usually normal, as is venous and arterial pressure. The left anterior hemithorax may bulge anteriorly because of right ventricular hypertrophy. The heart is generally normal in size, and a substernal right ventricular impulse can be detected. In about half the cases, a systolic thrill is felt along the left sternal border in the 3rd and 4th parasternal spaces. The systolic murmur is usually loud and harsh; it may be transmitted widely, especially to the lungs, but is most intense at the left sternal border. The murmur is generally ejection in quality at the upper sternal border, but it may sound more holosystolic toward the lower sternal border. It may be preceded by a click. The murmur is caused by turbulence through the right ventricular outflow tract. It tends to become louder, longer, and harsher as the severity of pulmonary stenosis increases from mild to moderate; however, it can actually become less prominent with severe obstruction, especially during a hypercyanotic spell. Either the 2nd heart sound is single, or the pulmonic component is soft. Infrequently, a continuous murmur may be audible, especially if prominent collaterals are present.
Roentgenographically, the typical configuration as seen in the anteroposterior view consists of a narrow base, concavity of the left heart border in the area usually occupied by the pulmonary artery, and normal heart size. The hypertrophied right ventricle causes the rounded apical shadow to be uptilted so that it is situated higher above the diaphragm than normal. The cardiac silhouette has been likened to that of a boot or wooden shoe (“coeur en sabot”) ( Fig. 2 ). The hilar areas and lung fields are relatively clear because of diminished pulmonary blood flow or the small size of the pulmonary arteries, or both. The aorta is usually large, and in about 20% of patients it arches to the right, which results in an indentation of the leftward-positioned air-filled tracheobronchial shadow in the anteroposterior view.
The electrocardiogram demonstrates right axis deviation and evidence of right ventricular hypertrophy. A dominant R wave appears in the right precordial chest leads (Rs, R, qR, qRs) or an RSR′ pattern. In some cases, the only sign of right ventricular hypertrophy may initially be a positive T wave in leads V3R and V1. The P wave is tall and peaked or sometimes bifid
Two-dimensional echocardiography establishes the diagnosis ( Fig. 3 ) and provides information about the extent of aortic override of the septum, the location and degree of the right ventricular outflow tract obstruction, the size of the proximal branch pulmonary arteries, and the side of the aortic arch. The echocardiogram is also useful in determining whether a PDA is supplying a portion of the pulmonary blood flow. In a patient without pulmonary atresia, echocardiography usually obviates the need for catheterization before surgical repair.
Cardiac catheterization demonstrates a systolic pressure in the right ventricle equal to systemic pressure. If the pulmonary artery is entered, the pressure is markedly decreased, although crossing the right ventricular outflow tract, especially in severe cases, may precipitate a tet spell. Pulmonary arterial pressure is usually lower than normal, in the range of 5–10 mm Hg. The level of arterial oxygen saturation depends on the magnitude of the right-to-left shunt; in “pink tets,” systemic saturation may be normal, whereas in a moderately cyanotic patient at rest, it is usually 75–85%.
Selective right ventriculography best demonstrates the anatomy of the tetralogy of Fallot. Contrast medium outlines the heavily trabeculated right ventricle. The infundibular stenosis varies in length, width, contour, and distensibility ( Fig. 4 ). The pulmonary valve is usually thickened, and the annulus may be small. In patients with pulmonary atresia and VSD, the anatomy of the pulmonary vessels may be extremely complex; for example, there may be discontinuity between the right and left pulmonary arteries. Complete and accurate information regarding the anatomy of the pulmonary arteries and any collateral vessels (MAPCAs) is important when evaluating these children as surgical candidates.
Left ventriculography demonstrates the size of the left ventricle, the position of the VSD, and the overriding aorta; it also confirms mitral-aortic continuity, thereby ruling out a double-outlet right ventricle. Aortography or coronary arteriography outlines the course of the coronary arteries. In 5–10% of patients with the tetralogy of Fallot, an aberrant major coronary artery crosses over the right ventricular outflow tract; this artery must not be cut during surgical repair. Verification of normal coronary arteries is important when considering surgery in young infants who may need a patch across the pulmonary valve annulus. Echocardiography can usually delineate the coronary artery anatomy; angiography is reserved for cases in which questions remain.
Before correction, patients with the tetralogy of Fallot are susceptible to several serious complications. Fortunately, most children undergo palliation or, more often, complete repair in infancy, and these complications are rare. Cerebral thromboses, usually occurring in the cerebral veins or dural sinuses and occasionally in the cerebral arteries, are common in the presence of extreme polycythemia and dehydration. Thromboses occur most often in patients younger than 2 yr. These patients may have iron deficiency anemia, frequently with hemoglobin and hematocrit levels in the normal range (but too low for cyanotic heart disease). Therapy consists of adequate hydration and supportive measures. Phlebotomy and volume replacement with albumin or saline are indicated in extremely polycythemic patients who are symptomatic.
Brain abscess is less common than cerebral vascular events and extremely rare when most patients are repaired at young ages. Patients with a brain abscess are usually older than 2 yr. The onset of the illness is often insidious and consists of low-grade fever or a gradual change in behavior, or both. Some patients have an acute onset of symptoms that may develop after a recent history of headache, nausea, and vomiting. Seizures may occur; localized neurologic signs depend on the site and size of the abscess and the presence of increased intracranial pressure. CT or MRI confirms the diagnosis. Antibiotic therapy may help keep the infection localized, but surgical drainage of the abscess is usually necessary (see Chapter 603 ).
Bacterial endocarditis may occur in the right ventricular infundibulum or on the pulmonic, aortic, or, rarely, tricuspid valves. Endocarditis may complicate palliative shunts or, in patients with corrective surgery, any residual pulmonic stenosis or VSD. Antibiotic prophylaxis is essential before and after dental and certain surgical procedures associated with a high incidence of bacteremia (see Chapter 437 ).
Heart failure is not a usual feature in patients with the tetralogy of Fallot. It may occur in a young infant with “pink” or acyanotic tetralogy of Fallot. As the degree of pulmonary obstruction worsens with age, the symptoms of heart failure resolve and eventually the patient experiences cyanosis, often by 6–12 mo of age. These patients are at increased risk for hypercyanotic spells at this time.
An associated PDA may be present, and defects in the atrial septum are occasionally seen. A right aortic arch occurs in ≈20% of patients with the tetralogy of Fallot, and other anomalies of the pulmonary arteries and aortic arch may also be seen. Persistence of a left superior vena cava draining into the coronary sinus may be noted. Multiple VSDs are occasionally present and must be diagnosed before corrective surgery. Tetralogy of Fallot may also occur with an atrioventricular septal defect, often associated with Down syndrome.
Congenital absence of the pulmonary valve produces a distinct syndrome that is usually marked by signs of upper airway obstruction (see Chapter 428.1 ). Cyanosis may be absent, mild, or moderate; the heart is large and hyperdynamic; and a loud to-and-fro murmur is present. Marked aneurysmal dilatation of the main and branch pulmonary arteries results in compression of the bronchi and produces stridulous or wheezing respirations and recurrent pneumonia. If the airway obstruction is severe, reconstruction of the trachea at the time of corrective cardiac surgery may be required to alleviate the symptoms.
Absence of a branch pulmonary artery, most often the left, should be suspected if the roentgenographic appearance of the pulmonary vasculature differs on the two sides; absence of a pulmonary artery is often associated with hypoplasia of the affected lung. It is important to recognize the absence of a pulmonary artery because occlusion of the remaining pulmonary artery during surgery seriously compromises the already reduced pulmonary blood flow.
As one of the conotruncal malformations, the tetralogy of Fallot can be associated with the spectrum of lesions known as CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia). CATCH 22 includes patients with clinical features of the DiGeorge syndrome (hypocalcemia, thymic hypoplasia, mild facial anomalies) or the Shprintzen velocardiofacial syndrome (abnormal facies, cleft palate). Cytogenetic analysis using fluorescence in situ hybridization demonstrates deletions of a large segment of chromosome 22q11 known as the DiGeorge critical region. Deletion or mutation of the gene encoding the transcription factor Tbx1 has been implicated as a possible cause of DiGeorge syndrome.
Treatment of the tetralogy of Fallot depends on the severity of the right ventricular outflow tract obstruction. Infants with severe tetralogy require medical treatment and surgical intervention in the neonatal period. Therapy is aimed at providing an immediate increase in pulmonary blood flow to prevent the sequelae of severe hypoxia. The infant should be transported to a medical center adequately equipped to evaluate and treat neonates with congenital heart disease under optimal conditions. It is critical that oxygenation and normal body temperature be maintained during the transfer. Prolonged, severe hypoxia may lead to shock, respiratory failure, and intractable acidosis and will significantly reduce the chance of survival, even when surgically amenable lesions are present. Cold increases oxygen consumption, which places additional stress on a cyanotic infant, whose oxygen delivery is already limited. Blood glucose levels should be monitored because hypoglycemia is more likely to develop in infants with cyanotic heart disease.
Neonates with marked right ventricular outflow tract obstruction may deteriorate rapidly because, as the ductus arteriosus begins to close, pulmonary blood flow is further compromised. The intravenous administration of prostaglandin E1 (0.01–0.20 μg/kg/min), a potent and specific relaxant of ductal smooth muscle, causes dilatation of the ductus arteriosus and usually provides adequate pulmonary blood flow until a surgical procedure can be performed. This agent should be administered intravenously as soon as cyanotic congenital heart disease is clinically suspected and continued through the preoperative period and during cardiac catheterization.
Infants with less severe right ventricular outflow tract obstruction who are stable and awaiting surgical intervention require careful observation. Prevention or prompt treatment of dehydration is important to avoid hemoconcentration and possible thrombotic episodes. Paroxysmal dyspneic attacks in infancy or early childhood may be precipitated by a relative iron deficiency; iron therapy may decrease their frequency and also improve exercise tolerance and general well-being. Red blood cell indices should be maintained in the normocytic range. Oral propranolol (0.5–1 mg/kg every 6 hr) had been used more commonly in the past to decrease the frequency and severity of hypercyanotic spells, but with the excellent surgery available, surgical treatment is now indicated as soon as spells begin.
Infants with symptoms and severe cyanosis in the 1st mo of life have marked obstruction of the right ventricular outflow tract or pulmonary atresia. Two options are available in these infants. The first, more common in previous years, is a palliative systemic-to-pulmonary artery shunt performed to augment pulmonary artery blood flow. The rationale for this surgery, previously the only option for these patients, is to decrease the amount of hypoxia and improve linear growth, as well as augment growth of the branch pulmonary arteries. The second option is corrective open heart surgery performed in early infancy and even in the newborn period in critically ill infants. This approach has widespread acceptance with excellent short- and long-term results and carries the theoretical advantage in that early physiologic correction allows for improved growth of the branch pulmonary arteries. In infants with less severe cyanosis who can be maintained with good growth and absence of hypercyanotic spells, primary repair is performed electively at between 4 and 6 mo of age.
The modified Blalock-Taussig shunt is currently the most common aortopulmonary shunt procedure and consists of a Gore-Tex conduit anastomosed side to side from the subclavian artery to the homolateral branch of the pulmonary artery ( Fig. 5 ). Sometimes the shunt is brought directly from the ascending aorta to the main pulmonary artery and in this case is called a central shunt. The Blalock-Taussig operation can be successfully performed in the newborn period with shunts 3–4 mm in diameter and has also been used successfully in premature infants.
Figure 5 Physiology of a Blalock-Taussig shunt in a patient with the tetralogy of Fallot. Circled numbers represent oxygen saturation values. The intracardiac shunting pattern is as described for Figure 430-1 . Blood shunting left to right across the shunt from the right subclavian artery to the right pulmonary artery increases total pulmonary blood flow and results in a higher oxygen saturation than would exist without the shunt
Postoperative complications after a Blalock-Taussig shunt include chylothorax, diaphragmatic paralysis, and Horner syndrome. Chylothorax may require repeated thoracocentesis and, on occasion, reoperation to ligate the thoracic duct. Diaphragmatic paralysis from injury to the phrenic nerve may result in a more difficult postoperative course. Prolonged ventilator support and vigorous physical therapy may be required, but diaphragmatic function usually returns in 1–2 mo unless the nerve was completely divided. Surgical plication of the diaphragm may be indicated. Horner syndrome is usually temporary and does not require treatment. Postoperative cardiac failure may be caused by a large shunt; its treatment is described in Chapter 442 . Vascular problems other than a diminished radial pulse and occasional long-term arm length discrepancy are rarely seen in the upper extremity supplied by the subclavian artery used for the anastomosis.
After a successful shunt procedure, cyanosis diminishes. The development of a continuous murmur over the lung fields after the operation indicates a functioning anastomosis. A good continuous shunt murmur may not be heard until several days after surgery. The duration of symptomatic relief is variable. As the child grows, more pulmonary blood flow is needed and the shunt eventually becomes inadequate. When increasing cyanosis develops, a corrective operation should be performed if the anatomy is favorable. If not possible (because of hypoplastic branch pulmonary arteries) or if the 1st shunt lasts only a brief period in a small infant, a second aortopulmonary anastomosis may be required on the opposite side.
Corrective surgical therapy consists of relief of the right ventricular outflow tract obstruction by removing obstructive muscle bundles and by patch closure of the VSD. If the pulmonary valve is stenotic, a valvotomy is performed. If the pulmonary valve annulus is small or the valve is extremely thickened, a valvectomy may be performed, the pulmonary valve annulus split open, and a transannular patch placed across the pulmonary valve ring. Any previously established systemic-to-pulmonary shunt must be ligated and divided before full repair. The surgical risk of total correction in major centers is <5%.>transatrial-transpulmonary approach is routinely performed to reduce the long-term risks of a right ventriculotomy. Increased bleeding in the immediate postoperative period may be a complicating factor in extremely polycythemic patients.
After successful total correction, patients are generally asymptomatic and are able to lead unrestricted lives. Uncommon immediate postoperative problems include right ventricular failure, transient heart block, residual VSD with left-to-right shunting, and myocardial infarction from interruption of an aberrant coronary artery. Postoperative heart failure (particularly in patients with a transannular outflow patch) may require diuretics and a positive inotropic agent such as digoxin. The long-term effects of isolated, surgically induced pulmonary valvular insufficiency are unknown, but insufficiency is generally well tolerated. The majority of patients after tetralogy repair and all of those with transannular patch repairs have a to-and-fro murmur at the left sternal border, usually indicative of mild outflow obstruction and mild to moderate pulmonary insufficiency. Patients with more marked pulmonary valve insufficiency also have moderate to marked heart enlargement. Patients with a severe residual gradient across the right ventricular outflow tract may require reoperation, but mild to moderate obstruction is usually present and does not require reintervention.
Follow-up of patients 5–20 yr after surgery indicates that the marked improvement in symptoms is generally maintained. Asymptomatic patients nonetheless have lower than normal exercise capacity, maximal heart rate, and cardiac output. These abnormal findings are more common in patients who underwent placement of a transannular outflow tract patch and may be less frequent when surgery is performed at an early age. As these children move into adolescence and adulthood, some (more commonly those with transannular patches) will develop right ventricular dilation due to severe pulmonary regurgitation. Careful lifelong follow-up by a specialist in adult congenital heart disease is important. Serial echocardiography and magnetic resonance angiography (MRA) are valuable tools for assessing the degree of right ventricular dilation, the presence of right ventricular dysfunction, and the regurgitant fraction. Valve replacement is indicated for those patients with increasing right ventricular pathology.
Conduction disturbances can occur after surgery. The atrioventricular node and the bundle of His and its divisions are in close proximity to the VSD and may be injured during surgery. Permanent complete heart block after surgery is rare. When present, it should be treated by placement of a permanently implanted pacemaker. Even transient complete heart block in the immediate postoperative period is rare; it may be associated with an increased incidence of late-onset complete heart block and sudden death. Right bundle branch block after right ventriculotomy is quite common on the postoperative electrocardiogram. The duration of the QRS interval has been shown to predict both the presence of residual hemodynamic derangement and the long-term risk of sudden death. Research is ongoing to determine the effectiveness of biventricular pacing (in which a pacemaker is used to resynchronize the activation of the right and left ventricles) in improving hemodynamics in those patients with long ventricular conduction delays.A number of children have premature ventricular beats after repair of the tetralogy of Fallot. These beats are of concern in patients with residual hemodynamic abnormalities; 24-hr electrocardiographic (Holter) monitoring studies should be performed to be certain that occult short episodes of ventricular tachycardia are not occurring. Exercise studies may be useful in provoking cardiac arrhythmias that are not apparent at rest. In the presence of complex ventricular arrhythmias or severe residual hemodynamic abnormalities, prophylactic antiarrhythmic therapy is warranted. Re-repair is indicated if significant residual right ventricular outflow obstruction or severe pulmonary insufficiency is present.