Tetralogy of Fallot

Tetralogy of Fallot (TOF) is a congenital heart defect which is classically understood to involve four anatomical abnormalities of the heart (although only three of them are always present). It is the most [1] common cyanotic heart defect, and the most common cause of blue baby syndrome. It was described in 1672 by Niels Stensen, in 1773 by Edward Sandifort, and in 1888 by the French [2] physician tienne-Louis Arthur Fallot, after whom it is named.

Signs and symptoms

Digital clubbing with cyanotic nail beds in an adult with tetralogy of Fallot

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 [3] 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 increases systemic vascular resistance and allows for a temporary reversal of the shunt. [edit]Cause 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. Specific genetic associations include: JAG1
[4]

NKX2-5 ZFPM2 VEGF

[7]

[5]

[6]

It occurs slightly more often in males than in females. Embryology studies show that it is a result of anterior malalignment of the aorticopulmonary septum, resulting in the clinical combination of a VSD, pulmonary stenosis, and an overriding aorta. Right ventricular hypertrophy develops progressively from resistance to blood flow through the right ventricular outflow tract.

Pathophysiology
[edit]Primary

four malformations

"Tetralogy" denotes a four-part phenomenon in various fields, including literature, and the four parts the syndrome's name implies are its four signs. This is not to be confused with the similarly named teratology, a field of medicine concerned with abnormal development and congenital malformations, which thereby includes tetralogy of Fallot as part of its subject matter. As such, by definition, tetralogy of Fallot involves four heart malformations which present together:

Tetralogy of Fallot

Normal heart

Condition

Description

A:Pulmonary Infundibular Stenosis

A narrowing of the right ventricular outflow tract. It 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 [8] (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 [9] 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[10] pulmonary stenosis or subpulmonary obstruction.

B: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 [8] connected to the right ventricle.

C: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 [8] (septal hypertrophy) can narrow the margins of the defect.

D: 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 [11] to be a secondary anomaly, as the level of hypertrophy tends to increase with age.

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. Presumably, this arises from a unequal growth of the aorticopulmonary septum. The aorta is too large, thus "overriding," and this "steals" from the pulmonary artery, therefore stenosed. This then prevents ventricular wall closure, therefore VSD, and this increases the pressures on the right side, and so the R ventricle becomes bigger to handle the work. [edit]Additional

anomalies

In addition, tetralogy of Fallot may present with other anatomical anomalies, including: 1. stenosis of the left pulmonary artery, in 40% of patients 2. a bicuspid pulmonary valve, in 60% of patients 3. right-sided aortic arch, in 25% of patients 4. coronary artery anomalies, in 10% of patients 5. a patent foramen ovale or atrial septal defect, in which case the syndrome is sometimes called [12] a pentalogy of Fallot 6. an atrioventricular septal defect 7. partially or totally anomalous pulmonary venous return 8. 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.
[13]

[edit]Diagnosis

A CXR of a child with tetralogy of Fallot

Congenital heart defects are now diagnosed with echocardiography, which is quick, involves no radiation, is very specific, and can be done prenatally. Before more sophisticated techniques became available, chest x-ray was the definitive method of diagnosis. The abnormal "coeur-en-sabot" (boot-like) appearance of a heart with tetralogy of Fallot is classically visible via chest x-ray, although most infants with tetralogy may not show this [14] [15] finding. Absence of interstitial lung markings are another classic finding in tetralogy. [edit]Treatment [edit]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 betablockers such as propranolol, but acute episodes may require rapid intervention with morphine to reduce ventilatory drive and a vasopressor such as epinephrine, phenylephrine, or norepinephrine to increase blood pressure. Oxygen (100%) is effective in treating spells because it is a potent pulmonary vasodilator and systemic vasoconstrictor. This allows more blood flow to the lungs. There are also simple procedures such as squatting and 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 [16] deoxygenated blood entering the systemic circulation. [edit]Palliative

surgery

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 [17] 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, 1944 with dramatic results. The Potts shunt and the Waterston-Cooley shunt are other shunt procedures which were developed for the same purpose. These are no longer used. 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). [edit]Total
[18] [19][20]

surgical repair

The Blalock-Thomas-Taussig procedure, initially the only surgical treatment available for tetralogy of Fallot, was palliative but not curative. The first total repair of tetralogy of Fallot was done by a team led [21] by C. Walton Lillehei at the University of Minnesota in 1954 on a 11-year-old boy. Total repair on infants has had success from 1981, with research indicating that it has a comparatively low mortality [22] rate. Total repair of tetralogy of Fallot initially carried a high mortality risk. This risk has gone down steadily over the years. Surgery is now often carried out in infants one year of age or younger with less than 5% perioperative mortality. The open-heart surgery is designed (1) to relieve the right ventricular outflow tract stenosis by careful resection of muscle and (2) to repair the VSD with aGore-Tex patch or a homograft. Additional reparative or reconstructive surgery may be done on patients as required by their particular cardiac anatomy. (WARNING: Graphic): Child minutes after open heart surgery for Tetralogy of Fallot [edit]Epidemiology Tetralogy of Fallot occurs in approximately 400 per million live births. [edit]Prognosis 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 depend 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 later in adulthood. They require, therefore, follow up in specialized Adult Congenital Heart Disease centres. [edit]Notable
[23]

cases
[24]

Shaun White,

snowboarder and 2006 and 2010 Olympic gold medallist Australian cricketer
[26]

Beau Casson,

[25]

Dennis McEldowney,

New Zealand author and publisher

Max Page (actor), Volkswagen's "Little Darth Vader" from the 2011 Super Bowl commercial Henry F. Gilbert, American composer

[27]

Conor Russo, First person born with condition to subsequently pass divers medical and complete a successful open water dive