Tetralogy of Fallot
(TOF) is a congenital heart defect
which is classically understood to involve four anatomical abnormalities (although only three of them are always present). It is the most common cyanotic
heart defect, representing 55-70%, and the most common cause of blue baby syndrome
It was described in 1672 by Niels Stensen, in 1673 by Edward Sandifort, and in 1888 by the French physician Étienne-Louis Arthur Fallot, for whom it is named.
Primary four malformations
As classically described, tetralogy of Fallot involves four heart
malformations which present together:
- A ventricular septal defect (VSD): a hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum (the outlet septum), and in the majority of cases is single and large. In some cases thickening of the septum (septal hypertrophy) can narrow the margins of the defect.
- Pulmonary stenosis: a narrowing of the right ventricular outflow tract and can occur at the pulmonary valve (valvular stenosis) or just below the pulmonary valve (infundibular stenosis). Infundibular pulmonic stenosis is mostly caused by overgrowth of the heart muscle wall (hypertrophy of the septoparietal trabeculae), however the events leading to the formation of the overriding aorta are also believed to be a cause. The pulmonic stenosis is the major cause of the malformations, with the other associated malformations acting as compensatory mechanisms to the pulmonic stenosis. The degree of stenosis varies between individuals with TOF, and is the primary determinant of symptoms and severity. This malformation is infrequently described as sub-pulmonary stenosis or subpulmonary obstruction.
- Overriding aorta: An aortic valve with biventricular connection, that is, it is situated above the ventricular septal defect and connected to both the right and the left ventricle. The degree to which the aorta is attached to the right ventricle is referred to as its degree of "override." The aortic root can be displaced toward the front (anteriorly) or directly above the septal defect, but it is always abnormally located to the right of the root of the pulmonary artery. The degree of override is quite variable, with 5-95% of the valve being connected to the right ventricle.
- Right ventricular hypertrophy: The right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen by chest X-ray. Due to the misarrangement of the external ventricular septum, the right ventricular wall increases in size to deal with the increased obstruction to the right outflow tract. This feature is now generally agreed to be a secondary anomaly, as the level of hypertrophy generally increases with age.
" (occasionally misspelled "tetro
logy") denotes a four-part thing in various fields, including literature
, and the four parts the syndrome's name implies are its four signs
Some confusion is possible with teratology, a field of medicine concerned with abnormal development and congenital malformations, which thereby includes the tetralogy of Fallot as part of its subject matter.
There is anatomic variation between the hearts of individuals with tetralogy of Fallot. Primarily, the degree of right ventricular outflow tract obstruction varies between patients and generally determines clinical symptoms and disease progression. In addition, tetralogy of Fallot may present with other anatomical anomalies, including:
- stenosis of the left pulmonary artery, in 40% of patients
- a bicuspid pulmonary valve, in 40% of patients
- right-sided aortic arch, in 25% of patients
- coronary artery anomalies, in 10% of patients
- an atrial septal defect, in which case the syndrome is sometimes called a pentalogy of Fallot
- an atrioventricular septal defect
- partially or totally anomalous pulmonary venous return
- forked ribs and scoliosis
Tetralogy of Fallot with pulmonary atresia (pseudotruncus arteriosus) is a severe variant in which there is complete obstruction (atresia) of the right ventricular outflow tract, causing an absence of the pulmonary trunk during embryonic development. In these individuals, blood shunts completely from the right ventricle to the left where it is pumped only through the aorta. The lungs are perfused via extensive collaterals from the systemic arteries, and sometimes also via the ductus arteriosus.
Epidemiology and etiology
Tetralogy of Fallot occurs in approximately 3 to 6 per 10,000 births and represents 5-7% of congenital heart defects. Its cause is thought to be due to environmental or genetic factors or a combination. It is associated with chromosome 22 deletions and diGeorge syndrome
. It occurs slightly more often in males than in females.
Embryology studies show that it is a result of anterior malalignment of the conal septum, resulting in the clinical combination of a VSD, pulmonary stenosis, and an overriding aorta. Right ventricular hypertrophy results from this combination, which causes resistance to blood flow from the right ventricle.
Pathophysiology and Symptoms
Tetralogy of Fallot results in low oxygenation
of blood due to the mixing of oxygenated and deoxygenated blood in the left ventricle via the VSD and preferential flow of the mixed blood from both ventricles through the aorta because of the obstruction to flow through the pulmonary valve. This is known as a right-to-left shunt. The primary symptom is low blood oxygen saturation with or without cyanosis
from birth or developing in the first year of life. If the baby is not cyanotic then it is sometimes referred to as a "pink tet". Other symptoms include a heart murmur which may range from almost imperceptible to very loud, difficulty in feeding, failure to gain weight, retarded growth and physical development, dyspnea on exertion, clubbing of the fingers and toes, and polycythemia
Children with tetralogy of Fallot may develop "tet spells". The precise mechanism of these episodes is in doubt, but presumably results from a transient increase in resistance to blood flow to the lungs with increased preferential flow of desaturated blood to the body. Tet spells are characterized by a sudden, marked increase in cyanosis followed by syncope, and may result in hypoxic brain injury and death. Older children will often squat during a tet spell, which cuts off circulation to the legs and therefore improves blood flow to the brain and vital organs.
The abnormal "coeur-en-sabot" (boot-like) appearance of a heart with tetralogy of Fallot is easily visible via chest x-ray, and before more sophisticated techniques became available, this was the definitive method of diagnosis. Congenital heart defects are now diagnosed with echocardiography, which is quick, involves no radiation, is very specific, and can be done prenatally.
Emergency management of tet spells
Prior to corrective surgery, children with tetralogy of Fallot may be prone to consequential acute hypoxia (tet spells), characterized by sudden cyanosis and syncope. These may be treated with beta-blockers
such as propranolol
, but acute episodes may require rapid intervention with morphine
to reduce ventilatory drive and phenylephrine
to increase blood pressure. Oxygen is ineffective in treating hypoxic spells because the underlying problem is lack of blood flow through the lungs and not oxygenation within the lungs. There are also simple procedures such as squatting in the knee-chest position which increases aortic wave reflection, increasing pressure on the left side of the heart, decreasing the right to left shunt thus decreasing the amount of deoxygenated blood entering the systemic circulation.
The condition was initially thought untreatable until surgeon Alfred Blalock
, cardiologist Helen B. Taussig
, and lab assistant Vivien Thomas
at Johns Hopkins University developed a palliative surgical procedure, which involved forming an anastomosis between the subclavian artery and the pulmonary artery (See movie "Something the Lord Made
"). It was actually Helen Taussig who convinced Alfred Blalock that the shunt was going to work. This redirected a large portion of the partially oxygenated blood leaving the heart for the body into the lungs, increasing flow through the pulmonary circuit, and greatly relieving symptoms in patients. The first Blalock-Thomas-Taussig shunt
surgery was performed on 15-month old Eileen Saxon
on November 29
with dramatic results.
The Pott shunt and the Waterson procedure are other shunt procedures which were developed for the same purpose.
Currently, Blalock-Thomas-Taussig shunts are not normally performed on infants with TOF except for severe variants such as TOF with pulmonary atresia (pseudotruncus arteriosus).
Total surgical repair
The Blalock-Thomas-Taussig procedure was the only surgical treatment until the first total surgical repair was performed in 1954. Between 1944 and when total repair became available at major surgical centers in the early 1960s, many infants and children were treated palliatively with Blalock-Thomas-Taussig procedures.
This first total repair was performed by C. Walton Lillehei at the University of Minnesota in 1954 on a 10-month boy. Total repair initially carried a high mortality risk which has consistently improved over the years. Surgery is now often carried out in infants 1 year of age or younger with a <5% perioperative mortality. The surgery generally involves making incisions into the heart muscle, relieving the right ventricular outflow tract stenosis by careful resection of muscle, and repairing the VSD using a Gore-Tex patch or a homograft. Additional reparative or reconstructive work may be done on patients as required by their particular anatomy.
Untreated, tetralogy of Fallot rapidly results in progressive right ventricular hypertrophy due to the increased resistance on the right ventricle. This progresses to heart failure (dilated cardiomyopathy) which begins in the right heart and often leads to left heart failure. Actuarial survival for untreated tetralogy of Fallot is approximately 75% after the first year of life, 60% by four years, 30% by ten years, and 5% by forty years.
Patients who have undergone total surgical repair of tetralogy of Fallot have improved hemodynamics and often have good to excellent cardiac function after the operation with some to no exercise intolerance (New York Heart Association Class I-II). Surgical success and long-term outcome greatly depends on the particular anatomy of the patient and the surgeon's skill and experience with this type of repair.
Ninety percent of patients with total repair as infants develop a progressively leaky pulmonary valve as the heart grows to its adult size but the valve does not. Patients also often have damage to the electrical system of the heart from surgical incisions, causing abnormalities as detected by EKG and/or arrhythmias.
Long-term follow up studies show that patients with total repair of TOF are at risk for sudden cardiac death and for heart failure. Therefore, lifetime follow-up care by an adult congenital cardiologist is recommended to monitor these risks and to recommend treatment, such as interventional procedures or re-operation, if it becomes necessary.
Antibiotic prophylaxis is indicated during dental treatment in order to prevent infective endocarditis.
Notable People born with Tetralogy of Fallot
- Shaun White, snowboarder and 2006 Olympic gold medallist
- Beau Casson, Australian cricketer
- Samuel Sanders (1937-1999), New York pianist
- Marc Ostrick, TV producer & director (documented his third open-heart surgery at age 27 in the film Open Hearted (2003))