Shabir Bhimji, MD, PhD,
Locum Cardiothoracic and Vascular Surgeon,
Saudi Arabia and Middle East Hospitals
Nothing to disclose.
Coauthor(s)
Mary C Mancini, MD, PhD,
Professor and Chief, Cardiothoracic Surgery,
Department of Surgery, Louisiana State University Health
Sciences Center-Shreveport
Nothing to disclose.
Specialty Editor(s)
Amer Suleman, MD,
Consultant in Electrophysiology and
Cardiovascular Medicine, Department of Internal Medicine,
Division of Cardiology, Medical City Dallas
Hospital
Nothing to disclose.
Francisco Talavera, PharmD, PhD,
Senior Pharmacy Editor,
eMedicine
eMedicine Salary Employment
Gary E Sander, MD, PhD, FACC, FAHA,
FACP,
Professor of Medicine, Tulane University
Heart and Vascular Institute; Director of In-Patient
Cardiology, Tulane Service, University
Hospital
Nothing to disclose.
Ronald J Oudiz, MD, FACP, FACC,
FCCP,
Professor of Medicine, University of
California, Los Angeles, David Geffen School of Medicine;
Director, Liu Center for Pulmonary Hypertension, Division of
Cardiology, LA Biomedical Research Institute at Harbor-UCLA
Medical Center
Park W Willis IV, MD,
Sarah Graham Distinguished Professor of
Medicine and Pediatrics, University of North Carolina at
Chapel Hill School of Medicine
Nothing to disclose.
Background
Tetralogy of Fallot (TOF) is one of the most common congenital heart disorders (CHDs). TOF is classified as a cyanotic heart disorder because the condition results in an inadequate flow of oxygenated blood to the systemic circulation. Patients with TOF initially present with cyanosis shortly after birth, thereby attracting early medical attention.
The 4 features typical of TOF include right ventricular outflow tract obstruction (RVOTO) (infundibular stenosis), ventricular septal defect (VSD), aorta dextroposition, and right ventricular hypertrophy. Occasionally, a few children also have an atrial septal defect, which makes up the pentad of Fallot. The basic pathology of tetralogy is due to the underdevelopment of the right ventricular infundibulum, which results in an anterior-leftward malalignment of the infundibular septum. This malalignment determines the degree of RVOTO.
The clinical features of TOF are generally typical, and a preliminary clinical diagnosis can almost always be made. Since most infants with this disorder require surgery, it is fortunate that the availability of cardiopulmonary bypass (CPB), cardioplegia, and surgical techniques is now well established. Most surgical series report excellent clinical results with low morbidity and mortality rates.
View Image
An opening in the right ventricle exposes ventricular septal defect.
View Image
Interrupted pledgetted sutures are used to close a ventricular septal defect.
Louis Arthur Fallot, after whom the name tetralogy of Fallot is derived, was not the first person to recognize the condition. Stensen first described TOF in 1672; however, it was Fallot who first accurately described the clinical and complete pathologic features of the defects.
Although the disorder was clinically diagnosed much earlier, no treatment was available until the 1940s. Cardiologist Helen Taussig recognized that cyanosis progressed and inevitably led to death in infants with TOF. She postulated that the cyanosis was due to inadequate pulmonary blood flow. Her collaboration with Alfred Blalock led to the first type of palliation for these infants. In 1944, Blalock operated on an infant with TOF and created the first Blalock-Taussig shunt between the subclavian artery and the pulmonary artery.
This pioneering surgical technique opened a new era in neonatal cardiac surgery. This was followed by development of the Potts shunt (from the descending aorta to the left pulmonary artery), the Glenn shunt (from the superior vena cava to the right pulmonary artery), and the Waterston shunt (from the ascending aorta to the right pulmonary artery).
Scott performed the first open correction in 1954. Less than half a year later, Lillehei performed the first successful open repair for TOF using controlled cross circulation, with another patient serving as oxygenator and blood reservoir. The following year, with the advent of CPB by Gibbons, another historic era of cardiac surgery was established. Since then, numerous advances in surgical technique and myocardial preservation have evolved in the treatment of TOF.
TOF occurs in 3-6 infants for every 10,000 births and is the most common cause of cyanotic CHD. The disorder is observed in other mammals, including horses and rats. TOF accounts for a third of all CHD in patients younger than 15 years. In most cases, TOF is sporadic and nonfamilial. The incidence in siblings of affected parents is 1-5%, and it occurs more commonly in males than in females. The disorder is associated with extracardiac anomalies such as cleft lip and palate, hypospadias, and skeletal and craniofacial abnormalities. Recent genetic studies indicate that in some patients with TOF there may be 22q11.2 deletion and other submicroscopic copy number alterations.[1]
The causes of most CHDs are unknown, although genetic studies suggest a multifactorial etiology. Prenatal factors associated with a higher incidence of TOF include maternal rubella (or other viral illnesses) during pregnancy, poor prenatal nutrition, maternal alcohol use, maternal age older than 40 years, and diabetes. Children with Down syndrome have a higher incidence of TOF.
Natural history
Early surgery is not indicated for all infants with TOF, although, without surgery, the natural progression of the disorder indicates a poor prognosis. The progression of the disorder depends on the severity of the RVOTO.
Without surgery, mortality rates gradually increase, ranging from 30% at age 2 years to 50% by age 6 years. The mortality rate is highest in the first year and then remains constant until the second decade. No more than 20% of patients can be expected to reach the age of 10 years, and fewer than 5-10% of patients are alive by the end of their second decade. Most individuals who survive to age 30 years develop congestive heart failure, although individuals whose shunts produce minimal hemodynamic compromise have been noted, albeit rarely, and these individuals achieve a normal life span.
As might be expected, individuals with TOF and pulmonary atresia have the worst prognoses, and only 50% survive to age 1 year and 8% to age 10 years.
If left untreated, patients with TOF face additional risks that include paradoxical emboli leading to stroke, pulmonary embolus, and subacute bacterial endocarditis.
The hemodynamics of TOF depend on the degree of RVOTO. The VSD is usually nonrestrictive, and the right and left ventricular pressures are equalized. If the obstruction is severe, the intracardiac shunt is from right to left, and pulmonary blood flow may be markedly diminished. In this instance, blood flow may depend on the patent ductus arteriosus or bronchial collaterals.
The clinical features are directly related to the severity of the anatomic defects. Most infants with TOF have difficulty with feeding, and failure to thrive is commonly observed. Infants with pulmonary atresia may become profoundly cyanotic as the ductus arteriosus closes unless bronchopulmonary collaterals are present. Occasionally, some children have just enough pulmonary blood flow and do not appear cyanotic; these individuals remain asymptomatic until they outgrow their pulmonary blood supply.
At birth, some infants with TOF do not show signs of cyanosis, but they may later develop episodes of bluish pale skin during crying or feeding (ie, Tet spells). A characteristic fashion in which older children with TOF increase pulmonary blood flow is to squat. Squatting is of diagnostic significance and is highly typical of infants with TOF. Squatting increases peripheral vascular resistance and thus decreases the magnitude of the right-to-left shunt across the VSD. Exertional dyspnea usually worsens with age. Occasionally, hemoptysis due to rupture of the bronchial collaterals may result in the older child.
The following factors can worsen cyanosis in infants with TOF:
Acidosis
Stress
Infection
Posture
Exercise
Beta-adrenergic agonists
Dehydration
Closure of the ductus
The predominant shunt is from right to left with flow across the VSD into the left ventricle, which produces cyanosis and an elevated hematocrit value. When the pulmonary stenosis is mild, bidirectional shunting may occur. In some patients, the infundibular stenosis is minimal, and the predominant shunt is from left to right, producing what is called a pink tetralogy. Although such patients may not appear cyanotic, they often have oxygen desaturation in the systemic circulation.
Physical examination
Most infants are smaller than expected for age. Cyanosis of the lips and nail bed is usually pronounced at birth; after age 3-6 months, the fingers and toes show clubbing.
A thrill is usually present anteriorly along the left sternal border. A harsh systolic ejection murmur is heard over the pulmonic area and the left sternal border. When the right ventricular outflow obstruction (eg, from pulmonary atresia) is moderate, the murmur may be inaudible. The S2 is usually single. During cyanotic episodes, murmurs may disappear, which is suggestive of lessened right ventricular outflow to the pulmonary arteries. In individuals with aortopulmonary collaterals, continuous murmurs may be auscultated.
Since tetralogy of Fallot (TOF) is a progressive disorder, most infants require some type of surgical procedure. The timing of complete surgical repair is dependent on numerous variables, including symptoms and any associated lesions (eg, multiple ventricular septal defect [VSD], pulmonary atresia).
Today, the trend is to perform a complete surgical procedure (often electively) before the age of 1 year and preferably by the age of 2 years.
Recent studies have shown, however, that surgery is preferably done at or about 12 months of age and most patients born with tetralogy of Fallot now thrive well into their adult years.[2]
Most surgeons now recommend the primary procedure, and current results are excellent. Infants with cyanosis are stabilized by administering prostaglandins (to maintain the ductus in an open state). The use of prostaglandins has significantly decreased the need to perform urgent surgery. Instead of performing systemic-to-pulmonary artery shunts on critically ill cyanotic-hypoxic infants, surgeons now have the luxury of having extra time to assess the patient's anatomy and to perform the primary procedure.
Primary repair avoids prolonged right ventricular outflow obstruction and the subsequent right ventricular hypertrophy, prolonged cyanosis, and postnatal angiogenesis.
Patients with tetralogy of Fallot (TOF) can present with a broad range of anatomic deformities. Fallot initially described 4 major defects consisting of (1) pulmonary artery stenosis, (2) ventricular septal defect (VSD), (3) deviation of the aortic origin to the right, and (4) right ventricular hypertrophy. Today, however, the most important features of TOF are recognized as (1) the right ventricular outflow tract obstruction (RVOTO), which is nearly always infundibular and/or valvular, and (2) an unrestricted VSD associated with malalignment of the conal septum.
Right ventricle outflow tract obstruction
Clinically, most patients with TOF have an increased resistance to right ventricle emptying because of the pulmonary outflow tract obstruction. The anterior displacement and rotation of the infundibular septum causes right ventricular obstruction of variable degree and location. The obstruction may be adjacent to the pulmonary valve, causing additional obstruction.
Pulmonary arteries
The pulmonary arteries can vary in size and distribution, and they may be atretic or hypoplastic. Rarely, the left pulmonary artery is absent. In some individuals, a varying degree of stenosis of the peripheral pulmonary arteries occurs, which further restricts pulmonary blood flow.
Pulmonary atresia results in no communication between the right ventricle and the main pulmonary artery; in this case, pulmonary blood flow is maintained by either the ductus or collateral circulation from the bronchial vessels. With minimal RVOTO, pulmonary vascular disease may develop secondary to excessive pulmonary blood flow from the large left-to-right shunt or large aortopulmonary collaterals. In up to 75% of children with TOF, some degree of pulmonary valve stenosis may occur. Stenosis is usually due to leaflet tethering rather than commissural fusion. The pulmonary annulus is narrowed in virtually every case.
Aorta
True dextroposition and abnormal rotation of the aortic root result in aortic overriding (ie, an aorta that, to varying degrees, originates from the right ventricle). In some cases, more than 50% of the aorta may thus originate from the right ventricle. A right aortic arch may occur, which may lead to an abnormal origin of the arch vessels.
Associated anomalies
Associated defects are also common. The coexistence of an atrial septal defect (ASD) occurs often enough to prompt its inclusion in a so-called pentalogy of Fallot. Other possible defects include patent ductus arteriosus, atrioventricular septal defects, muscular VSD, anomalous pulmonary venous return, anomalous coronary arteries, absent pulmonary valve, aorticopulmonary window, and aortic incompetence.
The coronary anatomy may also be abnormal. Among these abnormalities is the origin of the left anterior descending (LAD) coronary artery from the proximal right coronary artery, which crosses the right ventricular outflow at variable distances from the pulmonary valve annulus. The anomalous LAD coronary artery is observed in 9% of TOF cases, and this abnormality makes placement of a patch across the pulmonary annulus risky, possibly requiring an external conduit. During the VSD repair, the anomalous LAD coronary artery is prone to injury. Occasionally, all coronary arteries arise from a single left main coronary ostium.
Hemoglobin and hematocrit values are usually elevated in proportion to the degree of cyanosis. The oxygen saturation in the systemic arterial blood typically varies from 65-70%. All patients with TOF who experience significant cyanosis have a tendency to bleed because of decreased clotting factors and low platelet count. The usual findings are diminished coagulation factors. The total fibrinogen levels are also diminished and are associated with prolonged prothrombin and coagulation times.
Initially, chest radiographs may not reveal any abnormality; however, diminished vascularity in the lungs and diminished prominence of the pulmonary arteries gradually become apparent.
The hallmark of TOF is the classic boot-shaped heart (coeur en sabot).
Echocardiography
Today, ductus arteriosus, muscular VSD, or ASD are accurately diagnosed with color-flow Doppler echocardiography (ECG). The coronary anatomy can be revealed with some degree of accuracy, and valvar alterations can be detected with ease. In many institutions, echocardiography is the only diagnostic study used before surgery.
The use of ECG may be limited if multiple VSDs or coronary artery anomalies are present or if the distal pulmonary artery cannot be visualized adequately.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) provides good delineation of the aorta, right ventricular outflow tract, VSDs, right ventricular hypertrophy, and the pulmonary artery and its branches.
MRI can be used to measure intracardiac pressures, gradients, and blood flows.
Drawbacks to MRI include the need for prolonged imaging times and the requirement for sedation in small children to prevent motion artifacts. Additionally, sick infants cannot be observed when enclosed in an MRI tunnel.
Cardiac catheterization provides angiographic visualization of ventricular and pulmonary artery size. Catheterization also helps obtain pressure and oxygen saturation measurements in different chambers and identifies any possible shunts. In the presence of preexisting shunts, angiograms should be obtained before complete surgical repair.
Angiograms help identify coronary artery anomalies; however, catheterization is not mandatory in all patients. Cardiac catheterization is extremely useful if the anatomy cannot be completely defined by ECG, if disease in the pulmonary arteries is a concern, or if pulmonary vascular hypertension is possible.
View Image
This angiogram shows a catheter in the right ventricle—severe infundibular stenosis.
Surgery is the definitive treatment for the cyanotic patient with tetralogy of Fallot (TOF). The primary role of medical therapy is in preparation for surgery. Most infants have adequate saturations and usually undergo elective repair. In infants with acute cyanotic episodes, placing them in a knee-chest position may prove helpful in addition to administering oxygen and intravenous morphine. In severe episodes, intravenous propranolol (Inderal) may be administered, which relaxes the infundibular muscle spasm causing RVOTO. Progressive hypoxemia and the occurrence of cyanotic spells are indications for early surgery. Asymptomatic infants need no special medical treatment.
Factors that increase the risk for early repair of TOF include the following:
Low birth weight
Pulmonary artery atresia
Major associated anomalies
Multiple previous surgeries
Absent pulmonary valve syndrome
Young age
Old age
Severe annular hypoplasia
Small pulmonary arteries
High peak right ventricular–to–left ventricular pressure ratio
Multiple VSDs
Coexisting cardiac anomalies
Palliative procedures
The goals of palliation are to increase pulmonary blood flow independent of ductal patency and to allow pulmonary artery growth and even total correction. Occasionally, an infant with pulmonary atresia or an anomalous LAD coronary artery that crosses the right ventricular outflow tract may not be a surgical candidate for establishing transannular right ventricle–to–pulmonary artery continuity and may require placement of a conduit.
Although artificial conduits can be used, infants with extremely small pulmonary arteries may not tolerate total correction in infancy. These infants may require palliation instead of corrective surgery. Various types of palliative procedures have been developed, but the current procedure of choice is the Blalock-Taussig shunt.
The Potts shunts has been abandoned because of a tendency toward increased pulmonary blood flow and increasing difficulty with takedown at the time of corrective surgery. The Waterston shunt is sometimes used, but it also increases pulmonary artery blood flow. This shunt is more related to pulmonary artery stenosis, which generally requires reconstruction. The Glenn shunt is no longer used because of difficulty in performing a subsequent definitive repair.
Given the problems associated with the aforementioned shunts, placement of the modified Blalock-Taussig shunt (using a Gore-Tex graft between the subclavian artery and pulmonary artery) is the procedure of choice. Advantages of the modified Blalock-Taussig shunt include (1) preservation of the subclavian artery, (2) suitability for use on either side, (3) good relief of cyanosis, (4) easier control and closure at time of primary repair, (5) excellent patency rate, and (6) decreased incidence of iatrogenic pulmonary/systemic artery trauma.
View Image
This image shows completed blocking with a Taussig shunt.
View Image
This image shows a closed ventricular septal defect and closure of right ventriculotomy with Gore-Tex.
View Image
Gore-Tex is used for complete closure of right ventriculotomy.
The mortality rate is reportedly less than 1% when placing this shunt. However, the Blalock-Taussig shunt elicits a few complications, including hypoplasia of the arm, digital gangrene, phrenic nerve injury, and pulmonary artery stenosis.
The longevity of palliation after shunt placement varies according to the patient's age at the time of surgery and the type of shunt.
Other forms of palliation that are rarely used today include patching of the right ventricular outflow tract without cardiopulmonary bypass (CPB). This procedure can cause destruction of the pulmonary valve and significant intrapericardial adhesions, and the increased pulmonary artery blood flow can result in congestive heart failure; therefore, its role is limited to treatment of infants with TOF complicated by pulmonary atresia and/or hypoplasia of the pulmonary artery.
In very ill neonates with multiple medical problems, balloon pulmonary valvulotomy has been shown to increase oxygen saturation, thus obviating the need for emergency palliative surgery. However, perforation of the pulmonary artery is a risk with this procedure in neonates. A recent study indicates that shunting or primary repair of neonates with symptomatic TOF prduces similar mortality and results.[3]
Corrective surgery
Primary correction is the ideal operation for treatment of TOF and is usually performed under CPB. The aims of the surgery are to close the VSD, to resect the area of infundibular stenosis, and to relieve the RVOTO. Before CPB is initiated, previously placed systemic-to-pulmonary artery shunts are isolated and taken down. Patients then undergo CPB. Associated anomalies, such as ASD or patent foramen ovale, are closed.
All infants undergoing open-heart procedures are sent to the pediatric intensive care unit. Hemodynamic parameters must be followed postoperatively. All infants initially remain intubated on a ventilator until cardiac and respiratory status stabilize. To maintain systemic peripheral perfusion, adequate cardiac output and atrial pacing may be required. Patients should be weighed daily to follow volume status. Patients with heart block should have temporary atrioventricular pacing. If intrinsic conduction has not returned in 5-6 days, the patient probably needs a permanent pacemaker.
Results
The outcome of surgical repair is excellent with minimal morbidity and mortality. To date, no difference in operative mortality rates has been noted between transventricular and transatrial approaches.
The occasional patient has an elevated right ventricle–to–left ventricle pressure ratio. This may be due to a number of causes including a residual VSD, pulmonary artery stenosis, and pulmonary artery and valve atresia. These patients tend to do poor and echocardiography (ECHO) is warranted to find the cause. Surgical revision may be required to correct the etiology of the high RV pressures. As in previous studies, it is now apparent that preservation of pulmonary annulus can decrease the rate of reoperation.
With improved techniques, excellent results with early 1-stage repair in infants have been reported. Overall, the mortality rate in most series is 1-5% when the repair is performed primarily or after a systemic-to-pulmonary artery shunt. Similarly, the mortality rate of infants undergoing palliative shunt placement is low (0.5-3%). The survival rate at 20 years is approximately 90-95%.
Improved techniques of myocardial protection with hypothermia, cardioplegia, and even total circulatory arrest are providing excellent results by enabling more precise anatomic repairs in younger infants. Nevertheless, infants receiving complete correction before age 1 year have an increased risk compared with patients older than 1 year.
Revision/reoperation
The literature suggests that approximately 5% of individuals will need a revision/reoperation at some point. Indications for early reoperation include a residual VSD or a residual RVOTO.
Residual VSDs are poorly tolerated in patients with TOF because these individuals cannot tolerate an acutely imposed volume overload. Small, residual VSDs are common after TOF repair and are usually clinically insignificant. A residual VSD with a 2:1 shunt or an RVOTO of greater than 60 mm Hg is an urgent indication for reoperation. Surgery can be performed with low risk and can result in dramatic improvements. Occasionally, pulmonary valve insufficiency may increase and may be associated with right ventricular failure. Recurrent RVOTO may be due to muscular fibrosis or hypertrophy. This problem is generally treated with a pulmonary valve replacement. Porcine valves are preferred over mechanical valves because they have less tendency to thrombose.
Early postoperative complications include the creation of heart block and residual ventricular septal defects (VSDs). Ventricular arrhythmias are more common and are reportedly the most frequent cause of late postoperative death. Sudden death from ventricular arrhythmias has been reported in 0.5% of individuals within 10 years of repair. The arrhythmias are thought to occur in fewer than 1% of patients having an early operation. As with most heart surgery, the risk of endocarditis is lifelong, but the risk is much less than in a patient with an uncorrected tetralogy of Fallot.
In the present era of cardiac surgery, children with simple forms of tetralogy of Fallot (TOF) enjoy good long-term survival with an excellent quality of life. Late outcome data suggest that most survivors are in New York Heart Association classification I, although maximal exercise capability is reduced in some. Sudden death from ventricular arrhythmias has been reported in 1-5% of patients at a later stage in life, and the cause remains unknown. The surgical procedures are still palliative, and continued cardiac monitoring into adult life is necessary.
Today, some tetralogy of Fallot patients have survived for more than 15-20 years after their first operation. The major problem encountered by these individuals is the development of pulmonary valvular regurgitation. It appears that a number of these individuals require pulmonary valve replacement.[4] Most individuals receive a pericardial homograft and only time will tell how long these valves will last. However, the last decade has seen great advances in percutaneous technology and tissue engineering and perhaps the role of surgery may decline.[5]
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}