Tetralogy of Fallot

Introduction

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.

History of the Procedure

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.
Frequency

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.
Etiology

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. For more information on heart failure, see the Medscape Resource Center Heart Failure.
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. For more information on stroke, see the Medscape Resource Center Stroke/Cerebrovascular Disease.
Pathophysiology

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.
Presentation

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.

Indications

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.

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.

Relevant Anatomy

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.
Contraindications

Contraindications to primary repair in tetralogy of Fallot (TOF) include the following:

The presence of an anomalous coronary artery
Very low birth weight
Small pulmonary arteries
Multiple VSDs
Multiple coexisting intracardiac malformations

http://emedicine.medscape.com/article/163628-overview