Tetralogy of Fallot
(See also Overview of Congenital Cardiovascular Anomalies.)
Tetralogy of Fallot consists of 4 features: a large ventricular septal defect, right ventricular outflow tract and pulmonary valve obstruction, right ventricular hypertrophy, and over-riding of the aorta. Symptoms include cyanosis, dyspnea with feeding, poor growth, and hypercyanotic "tet" spells (sudden, potentially lethal episodes of severe cyanosis). A harsh systolic murmur at the left upper sternal border with a single 2nd heart sound (S2) is common. Diagnosis is by echocardiography. Cardiac catheterization may be done. Definitive treatment is surgical repair.
Tetralogy of Fallot (see Figure: Tetralogy of Fallot.) accounts for 7 to 10% of congenital heart anomalies. Associated anomalies include right aortic arch (25%), abnormal coronary artery anatomy (5%), stenosis of the pulmonary artery branches, presence of aorticopulmonary collateral vessels, patent ductus arteriosus, complete atrioventricular septal defect, atrial septal defect, additional muscular ventricular septal defects (VSDs), and aortic valve regurgitation.
Tetralogy of Fallot.
The ventricular septal defect is typically large; thus, systolic pressures in the right and left ventricles (and in the aorta) are the same. Pathophysiology depends on the degree of right ventricular outflow obstruction. A mild obstruction may result in a net left-to-right shunt through the VSD; a severe obstruction causes a right-to-left shunt, resulting in low systemic arterial saturation (cyanosis) that is unresponsive to supplemental oxygen.
In some children with unrepaired tetralogy of Fallot, most often those several months up to 2 yr of age, sudden episodes of profound cyanosis and hypoxia (tet spell) may occur, which may be lethal. A spell may be triggered by any event that slightly decreases oxygen saturation (eg, crying, defecating) or that suddenly decreases systemic vascular resistance (eg, playing, kicking legs when awakening) or by sudden onset of tachycardia or hypovolemia.
The mechanism of a tet spell remains uncertain, but several factors are probably important in causing an increase in right-to-left shunting and a fall in arterial saturation. Factors include an increase in right ventricular outflow tract obstruction, an increase in pulmonary vascular resistance, and/or a decrease in systemic resistance—a vicious circle caused by the initial fall in arterial Po2, which stimulates the respiratory center and causes hyperpnea and increased adrenergic tone. The increased circulating catecholamines then stimulate increased contractility, which increases outflow tract obstruction.
Neonates with severe right ventricular outflow obstruction (or atresia) have severe cyanosis and dyspnea during feeding, leading to poor weight gain. Neonates with mild obstruction may not have cyanosis at rest.
Tet spells may be precipitated by activity and are characterized by paroxysms of hyperpnea (rapid and deep respirations), irritability and prolonged crying, increasing cyanosis, and decreasing intensity of the heart murmur. The spells occur most often in young infants; peak incidence is age 2 to 4 mo. A severe spell may lead to limpness, seizures, and occasionally death. During play, some toddlers may intermittently squat, a position that increases systemic vascular resistance and aortic pressure, which decreases right-to-left ventricular shunting and thus raises arterial oxygen saturation.
Auscultation detects a harsh grade 3 to 5/6 systolic ejection murmur at the left mid and upper sternal border (see Table: Heart Murmur Intensity). The murmur in tetralogy is always due to the pulmonary stenosis; the ventricular septal defect is silent because it is large and has no pressure gradient. The 2nd heart sound (S2) is usually single because the pulmonary component is markedly reduced. A prominent right ventricular impulse and a systolic thrill may be present.
Diagnosis of tetralogy of Fallot is suggested by history and clinical examination, supported by chest x-ray and ECG, and established by 2-dimensional echocardiography with color flow and Doppler studies. Chest x-ray shows a boot-shaped heart with a concave main pulmonary artery segment and diminished pulmonary vascular markings. A right aortic arch is present in 25%.
ECG shows right ventricular hypertrophy and may also show right atrial hypertrophy.
Cardiac catheterization is rarely needed, unless there is suspicion of a coronary anomaly that might affect the surgical approach (eg, anterior descending arising from the right coronary artery) that cannot be clarified with echocardiography.
Neonates with severe cyanosis may be palliated with an infusion of prostaglandin E1 (0.01 to 0.1 mcg/kg/min IV) to open the ductus arteriosus and thereby increase pulmonary blood flow.
Tet spells require immediate intervention. The first steps are to place infants in a knee-chest position (older children usually squat spontaneously and do not develop tet spells), establish a calm environment, and give supplemental oxygen. If the spell persists, standard medical therapy includes morphine 0.1 to 0.2 mg/kg IV or IM, IV fluids for volume expansion and, if metabolic acidosis is present, sodium bicarbonate 1 mEq/kg IV.
Intranasal midazolam and intranasal fentanyl are alternatives to morphine and have the advantage of not requiring IV access.
Other options for more severe or prolonged tet spells include phenylephrine starting at 5 to 20 mcg/kg IV every 10 to 15 min as needed (to a maximum of 500 mg) followed by an infusion of 0.1 mcg/kg/min (to a maximum of 5 mcg/kg/min) if needed and beta-blockers (propranolol 0.015 mg/kg IV infused over 10 min (to a maximum of 1mg) or esmolol 0.1 to 0.5 mg/kg IV over 1 min followed by an infusion of 25 to 100 mcg/kg/min if needed. If these measures do not control the spell, systemic BP can be increased with ketamine 0.5 to 3 mg/kg IV or 2 to 3 mg/kg IM (ketamine also has a beneficial sedating effect).
Ultimately, if the preceding steps do not relieve the spell or if the infant is rapidly deteriorating, tracheal intubation with muscle paralysis and general anesthesia, extracorporeal membrane oxygenation (ECMO), or urgent surgical intervention may be necessary. Propranolol 0.25 to 1 mg/kg po q 6 h may prevent recurrences, but most experts feel that even one significant spell indicates the need for expeditious surgical repair.
Complete repair of tetralogy of Fallot consists of patch closure of the ventricular septal defect, widening of the right ventricular outflow tract with muscle resection and pulmonary valvuloplasty, and a limited patch across the pulmonic annulus or main pulmonary artery if necessary. Surgery is usually done electively at age 3 to 6 mo but can be done at any time if symptoms are present.
In some neonates with low birth weight or complex anatomy, initial palliation may be preferred to complete repair; the usual procedure is a modified Blalock-Taussig shunt, in which the subclavian artery is connected to the ipsilateral pulmonary artery with a synthetic graft.
Perioperative mortality rate for complete repair is < 5% for uncomplicated tetralogy of Fallot. For untreated patients, survival rates are 55% at 5 yr and 30% at 10 yr.
Endocarditis prophylaxis is recommended preoperatively but is required only for the first 6 mo after repair unless there is a residual defect adjacent to a surgical patch or prosthetic material.
Tetralogy of Fallot involves a large ventricular septal defect (VSD), right ventricular outflow tract and pulmonary valve obstruction, and over-riding of the aorta.
Pulmonary blood flow is decreased, the right ventricle hypertrophies, and unoxygenated blood enters the aorta via the VSD.
Manifestations depend on the degree of right ventricle outflow obstruction; severely affected neonates have marked cyanosis, dyspnea with feeding, poor weight gain, and a harsh grade 3 to 5/6 systolic ejection murmur.
Tet spells are sudden episodes of profound cyanosis and hypoxia that may be triggered by a fall in oxygen saturation (eg, during crying, defecating), decreased systemic vascular resistance (eg, during playing, kicking legs), or sudden tachycardia or hypovolemia.
Give neonates with severe cyanosis an infusion of prostaglandin E1 to open the ductus arteriosus.
Place infants with tet spells in the knee-chest position and give oxygen; sometimes, opioids (morphine or fentanyl), volume expansion, sodium bicarbonate, beta-blockers (propranolol or esmolol), or phenylephrine may help.
Repair surgically at 3 to 6 mo or earlier if symptoms are severe.
Drug NameSelect Trade
fentanylACTIQ, DURAGESIC, SUBLIMAZE
morphineDURAMORPH PF, MS CONTIN
phenylephrineNo US brand name