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Articles » Cardiovascular » Tetralogy of Fallot
2002-05-31-12 Tetralogy of Fallot © Sierra www.thefetus.net/
Tetralogy of Fallot

Revised from  2001-06-28-  by

Jose Sierra, MD

Medellin, Colombia 

Angela Appendino Capelanes, MD*, Philippe Jeanty, MD, PhD#

*Centro de Atendimento Materno-Fetal, Aracatuba Sao Paulo, Brazil;  #Nashville, TN 

Synonyms: None

Definition:

Tetralogy of Fallot is a group of congenital heart malformations responsible for cyanosis after birth that has four mayor components:

·        Pulmonary valve stenosis

·        High interventricular septal defect

·        Dextroposition of the aortic artery with its aortic root overriding the ventricular septal defect (the crest of the ventricular septum)

·        Concentric hypertrophy or the right ventricle.

The pulmonary stenosis is valvular in 25% of the cases, infundibular in 25%, and both valvular and infundibular in 50% of the cases. This pulmonary stenosis is highly variable, from mild stenosis to cases in which pulmonary valve atresia is present. These cases are called “pseudotruncus”, since they functionally behave as a common truncus. A fibromuscular or fibrous hypertrophy of the infundibular region can be seen in the infundibular stenosis. When this fibrous hypertrophy is located below the infundibulum, the space between the hypertrophied ring and the valve is called the “infundibular camera” or “third ventricle” or “double-chamber right ventricle”.

The interventricular septal defect or communication is perimembranous and usually wide, with an overriding aorta which will determine the degree of cyanosis of the affected individuals after birth.

Four types of Fallot have been described depending on the severity or extent of the anatomical defects.

  1. The “extreme” Fallot or “pseudotruncus”, in which the pulmonary stenosis is so severe that the pulmonary artery is almost atresic or absent.
  2. The “classic” Fallot, in which important pulmonary stenosis and overriding of the aorta above the ventricular septal defect can be seen.
  3. The “pink” Fallot, in which a small defect is seen: a mild pulmonic stenosis and a discrete overriding of the aorta over the interventricular septal defect.
  4. The “pentalogy” of Fallot, is that in which an interauricular septal defect is seen in addition to the four typical components [1] , [2] , [3] , [4] .

 

History: The Danish, Nicholas Steno was who first referred to tetralogy of Fallot in 1673, and then Edward Sandifort in the 1673. In 1888, the French physician Louis Arthur Fallot made the first complete description of this congenital heart disease.1 ,2 ,3 He called it “the maladie bleue”, a reference to the cyanosis of the children affected with the disease. Birmingham later made a reference to the “pentalogy” [5] . Other cases had been described by the famous William Hunter. He wrote: “The passage from the right ventricle into the pulmonary artery, which should have admitted a finger, was not so wide as a goose quill; and there was a hole in the partition of the two ventricles, large enough to pass the thumb from one to the other. . . The greatest part of the blood in the right ventricle was driven with that of the left ventricle into the aorta, or great artery, and so lost all the advantage which it ought to have had from breathing”. [6]

Incidence: 4:10.000 live births3 , [7] , [8] .

Prevalence: Tetralogy of Fallot represents 15% of all the congenital heart disease, and is the most common of the cyanotic congenital malformations1 , representing 55-70%. In a recent study by Boudjemline et al., in a series of 337 cases of conotruncal heart disease, tetralogy of Fallot made up 56% of these cases, vascular malposition 16%, coarctation with or without interruption of the aortic arch 14%, truncus arteriosus 9% and agenesis of the pulmonary valves 5%7 .

Congenital right heart lesions (including tetralogy of Fallot, pulmonary atresia with intact ventricular septum, Ebstein’s anomaly and dysplastic tricuspid valve) account for about 19% of congenital cardiac anomalies. [9]

Sex ratio: Slight predominance of males over females3 .

Etiology: almost completely unknown1 ,2 ,3 . The etiology of congenital heart disease is not well established and the implications for recurrence, genetics and environment are little known. Several genes, separately or in combination, could contribute to these defects. The 22q11 deletion has been associated with congenital conotruncal heart defects, as well an intrafamilial variability of cardiac involvement. There is a reported case of monozygotic twins, both with tetralogy of Fallot, in whom prenatal diagnosis found 22q11 micro deletion. Alcohol, anti-convulsivants, thalidomide and maternal hyperphenylalaninemia and phenylketonuria have been described as teratogens to tetralogy of Fallot4 , [10] , [11] , [12] , [13] .

Pathogenesis and embryogenesis:  Tetralogy of Fallot is due to an abnormal embryological development of the heart in which an unequal conotruncal division results in a small pulmonary artery and a great aortic artery. The normal rotational process of the conotruncal septum does not take place the way it should, and a lesser than 180-degree rotary motion is responsible for the dextroposition of the aortic artery. However, the pulmonary artery remains in an anterior position in relation to the aorta. This differentiates tetralogy of Fallot from complete transposition of the great vessels, where the position of the pulmonary and aortic arteries is inverted. The incomplete embryologic rotational process of the conotruncal septum explains the lack of alignment of this septum with the interventricular septum in tetralogy of Fallot. Under normal circumstances one septum is continuous with the other. The abnormal alignment process produces a defect of tissue between the septa, causing the interventricular communication. This usually large defect is unrestrictive and ensures equal ventricular pressures. The incomplete rotational process of the aortic artery explains its dextroposition, its overriding location above the interventricular septum and its relationship with the right ventricle.

Pulmonary infundibular stenosis is at least partly due to anterior deviation of the infundibular septum, which in itself narrows the subpulmonary outflow tract. This furthers the malalignment of the septa. 

The variable resistance created by the stenotic pulmonary artery, prevents the venous flow of the right heart from moving freely towards the pulmonary circulation, and the wide interventricular defect allows it into the left ventricle and aorta, creating the right to left shunt. In utero, this is not a problem for the fetus, since normal blood oxygenation takes place in the utero-placental unit.

In the classic Fallot, systemic hypoxia is the most important problem after birth and the admixture explains the cyanosis in the affected individuals. The severity of both, the pulmonary artery stenosis and the aortic overriding above the interventricular septum, will determine the degree of hypoxia and cyanosis of the newborn. In mild cases cyanosis may be absent. The worst the pulmonary stenosis the greater the size of the aortic artery, because it will have both, its own flow and the corresponding flow of the pulmonary artery.

After birth, since the interventricular septal defect is usually wide, the right ventricle is subjected to the left ventricular and aortic pressures. In addition, the right ventricle works against resistance to flow, due to the pulmonary stenosis. These two facts produce adaptational overload and systemic pressures within the right ventricle (right ventricular hypertension). This causes the concentric hypertrophy of the right ventricle seen in tetralogy of Fallot after birth1 ,2 ,3 ,4 .

Diagnosis: Isolated septal defects are the most difficult lesions to diagnose, and can reach almost 62% of false negatives [14] , [15] . The diagnosis of conotruncal anomalies has high degree of accuracy, but the definition of the relationship of the great arteries can be difficult in some cases. In particular, the assessment of the amount of overriding and the differential diagnosis with a double-outlet right ventricle can be difficult. Hypertrophy of the right ventricle and cardiac failure is not seen in the fetus and occurs only after the birth24. Although two-dimensional real-time ultrasound is the primary method of diagnosis, the accuracy of prenatal diagnosis of congenital heart diseases may be improved by color Doppler flow mapping [16] , [17] . Color Doppler flow mapping may allow screening for flow abnormalities of the fetal heart and exacts localization of sample volume by pulsed wave Doppler in area of abnormal flow pattern is possible. Furthermore, the traditional cytogenetic analysis should be complemented, by fluorescence in situ hybridization (FISH) for a deletion 22q11, in pregnancies with a high risk [18] , [19] .

Sonographic findings: 

The ultrasound diagnosis is difficult, especially in a four-chamber view, where the interventricular defect and the overriding aorta may not be easily seen. Four-chamber view is generally normal (only 31% of cardiac malformations are associated with an abnormal four chamber view) [20] , [21] , [22] . Authors highly recommend a three vessel view of the fetal upper mediastinum, that is as simple to obtain as the four chamber-views and demonstrates the main pulmonary, ascending aorta and superior vena cava, in cross or oblique sections. These vessels should be evaluated in terms of size, number, arrangement and alignment [23] . Aortic root dilatation, not seen in all cases, has been considered a marker of tetralogy of fallot27 , but a normal size does not exclude the diagnosis[24] .

Hydrops fetalis and polyhydramnios can occasionally be seen, especially in severe cases with absent pulmonary valve (which occurs in 3-6% of patients with tetralogy of Fallot) and pulmonary artery aneurysm, in which the mediastinal structures can be compressed23 , [25] ,[26] , [27] . The aneurysm may be seen as a cystic, pulsatile dilatation, without definite valve echoes26 , [28] , [29] , [30] .

Color Doppler may demonstrate reverse flow in the ductus arteriosus to the main pulmonary artery (ductal-dependent circulation, which denotes poor prognosis) [31] . These sonographic findings provide an indirect sign of severe right ventricular outlet obstruction. In pulmonary stenosis and atresia, the stenotic jet, even small, is identified by demonstration of high velocities and turbulence in the main pulmonary artery.

The overriding of the aorta with blood entering from both ventricles into the aorta is visible as a “Y” shaped image in color Doppler during the systolic phase [32] , [33] . Pulmonary artery stenosis is not always present at initial ultrasound examination, but this finding can develop or worsen during in-utero life. The small pulmonary artery diameter is easy to see in the “let your fingers do the walking” view (a basal, short axis section of the heart) or in the 3-vessel-view23 ,24 . Main pulmonary artery size, main pulmonary artery/aortic diameter ratio and pattern of pulmonary artery growth may be predictive of the severity of postnatal pulmonary outflow obstruction. Pulmonary artery atresia and progressive pulmonary artery stenosis can develop in utero in some fetuses with tetralogy of Fallot [34] , [35] . During the prenatal period, the concentric hypertrophy of the right ventricle is not seen.

Four-chamber view is generally normal<![endif]> (only 31% of cardiac malformations are associated with an abnormal four chamber view),

 

 

The left outflow view (sometimes called the “Five-chamber view”) demonstrates the overriding of the aorta and the ventricular septal defect7,24. This is visible by noting an interruption of the normal continuity between the anterior wall of the ascending aorta and the interventricular septum (there is a 2.5 MB Window videoclip and a 2.5 MB Quicktime videoclip of this), which could be demonstrated by Doppler (There is a 2.4 MB videoclip of this)

 

 

 

 

Enlarged aortic root (a normal aortic diameter does not exclude tetralogy of Fallot), There is a 0.8 MB videoclip of this.

 

The "Let your fingers do the walking" view in:

       Normal                     Tetralogy of Fallot

The 3-vessel-view in 
      Normal                     Tetralogy of Fallot

Cyan = pulmonary artery

Red = aorta

Blue = superior vena cava

Small pulmonary artery diameter (pulmonary artery stenosis is not always present at initial ultrasound examination, but this finding can develop or worsen during pregnancy). This finding is easiest to notice in the “Let your fingers do the walking” section (a basal, short axis section of the heart) or in the 3-vessel-view.

 

 

 

Inverse ratio aorta/pulmonary (aorta is larger than pulmonary artery),

 

 

Valvular pulmonary stenosis,

 

 

No abnormality in the thickness of right ventricle,

 

 

Color-flow mapping in a long-axis view of aortic arch may show reverse flow in the duct (this finding denotes very poor prognosis),

 

 

Doppler shows high velocities and turbulence in the pulmonary artery (due to obstruction of blood flow in the right outflow tract).

 

 

The disease can be progressive and demonstrate various appearances during pregnancy. In some case the pulmonary stenosis can progress all the way to pulmonary valve atresia at birth[27].

 

Differential diagnosis: A defect of the endocardial cushions with atrioventricular canal should always be ruled out, as well as isolated pulmonic stenosis. Fetal syndromes and chromosomal anomalies should be excluded since they are present in 16-61% of cases with tetralogy of Fallot..Other differential diagnosis include Truncus arteriosus (see also Truncus arteriosus) or double-outlet right ventricle

Associated anomalies: There are associated malformations in approximately 8%, as well as an abnormal karyotype in 8% of all cases7 . The most consistent congenital heart associations are left superior vena cava, right aortic arch (20%), absence of ductus arteriosus (15%), absent pulmonary valve with pulmonary aneurysm, atrioventricular canals, and atrial septal defect (25%) that is present prenatally. In the postnatal period more than 50% of the patients will have a patent foramen ovale as an associated anomaly29 , [36] , [37] . Other reported anomalies include Prune Belly syndrome [38] and DiGeorge sequence [39]

Azancot et al. in a recent study of 44 cases of non-isolated tetralogy of Fallot, found genetic anomalies in 18 of the fetuses (10 trisomies, including five trisomies 21 and 5 structural abnormalities including 2 micro-deletions 22q11 and 1 deletion of chromosome 8p23.1 and 3 mendelian syndromes), with an overall incidence of malformations of 61% [40] .

Type

Anomalies

Cardiovascular

  • absent pulmonary valve
  • anomalies of the left heart
  • atrial septal defect
  • atrioventricular canal
  • ductus arteriosus
  • Infundibular hypertrophy
  • pulmonary hypoplasia/atresia
  • valvular agenesis
  • venous anomalies

Extracardiac abnormalities

  • Prune Belly
  • Shprintzen (velo-cardio-facial) syndrome
  • hypoparathyroidism
  • DiGeorge sequence

Chromosome anomalies

  • Trisomy 13
  • Trisomy 18
  • Trisomy 21
  • Monosomy X
  • micro-deletions 22q11
  • deletion of chromosome 8p23.1

Prognosis: In early life the prognosis will be determined by the presence of associated anomalies and fetal syndromes in which cases the survival rate is only 10%. In isolated cases of tetralogy of Fallot, the survival rate reaches 85%.

Those cases with severe pulmonary stenosis or atresia, aneurysm of the pulmonary artery associated with hydrops fetalis and polyhydramnios, and great overriding aorta above the interventricular septal defect, will eventually have cardiac failure and may die in utero. Those that do not die in utero will be cyanotic after birth and will have short life expectancy.

Those cases of mild to moderate pulmonary stenosis with discrete overriding aorta will have the best prognosis and surgical results. The cyanosis after birth may be gentle or absent, and a normal life span may be achieved.

 

Recurrence risk: In cases of a sibling with Tetralogy of Fallot, the recurrence risk is estimated in 2%7.

 

Management: No special treatment during pregnancy is offered. Careful thorough sonographic screening is highly recommended. Amniocentesis should be considered given the association with chromosomal anomalies and fetal syndromes7 . Labor and delivery should be undertaken under fetal and maternal surveillance. Surgical procedures may be palliative (designed to increase the pulmonary blood flow) or definitive (with intracardiac repair of the abnormal anatomy)1 ,2 ,3 .

Reviewer: Alicia Martin-Hirsel, MD, RDMS; Lilian Lopes, MD, PhD

References

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