Tetralogy of falsotQ21.3

Already in 1571 Nils Stensen described the Fallot tetralogy for the first time (Apitz 2015) and in 1866 Sir Thomas Bevill Peacock described the clinical picture anatomically and pathologically (Chopra 2013). The French pathologist Etienne Louis Arthur Fallot, after whom the Fallot tetralogy was finally named, coined the term "tetralogy" in 1888 (Chopra 2013).

Alfred Blalock performed the first surgical measure in 1944 in the form of palliative surgery (Apitz 2015) by connecting the subclavian and pulmonary arteries with a shunt (Schmid 2004).

The first correction of the tetralogy of Fallot by means of cross circulation was performed by Lillihei in 1954 and one year later by Kirklin with the help of the heart-lung machine (Schmid 2004).

In Fallot tetralogy there is a shift of the infundibulum septum to the right, anterocephalic. This displacement leads to various changes in the anatomy of the heart (see "Anatomy" below). The image is determined by the severity of the obstruction of the right-sided outflow tract (Kasper 2015).

Anatomy

According to Becker (1985), the primary malformation is due to a forward displacement in the area of the septal insertion of the infundibulum septum. As a result, the septum of the infundibulum lies in front of the legs of the septomarginal trabecula and not - as is usually the case - between the legs.

This in turn leads to the typical malformations such as

• Pulmonary stenosis:
  • more infundibular (at 50 % [Herold 2019])
  • more valvular (at 10 % [Herold 2019])
  • at both locations (at 30 % [Herold 2019])
  • less frequently supravalvular
  • 10 % have pulmonary atresia (Herold 2019)
• acute ventricular septal defect
• the aorta protruding over the ventricular septum defect (so-called riding aorta)
• compensatory hypertrophy of the right ventricle (Pinger 2019)

The pathophysiology depends on the severity of pulmonary stenosis (RVOTO) and the size of the ventricular septal defect (Pinger 2019).

Pathophysiology in RVOTO: venous blood does not flow through the lungs, but enters the systemic circulation directly through the ventricular septal defect. Depending on the size of the RVOTO, a slight to severe right-left shunt occurs (Herold 2019). The central pulmonary vessels are more or less hypoplastic due to the reduced pulmonary perfusion (Pinger 2019).

Pathophysiology in the presence of a ventricular septal defect: There is a pressure equalization between the right ventricle, the left ventricle and the aoota. This pressure equalization leads to a left-right shunt, just like in an isolated ventricular septal defect (Apitz 2005). A simultaneously existing Ductus Botalli improves hemodynamics by increasing lung perfusion (Pinger 2019).

With a prevalence of 4.7 / 10,000 births, the tetralogy of Fallot is the most common cyanotic congenital malformation (Briese 2010).

It accounts for 10 % of all congenital heart defects and 65 % of all congenital cyanotic heart defects (Herold 2019).

More male newborns are affected by the malformation. The sex ratio is m: w = 1.4: 1 (Herold 2019).

Approximately 280 children with a Fallot tetralogy are operated on in Germany every year. Half of them are < 1 year (Schmid 2004).

Associated malformations of the cardiovascular system:

In approx. 20 % to 30 % there are further malformations such as:

• Anomaly of the coronaries (4 % - 5 % [Apitz 2005])
• right aortic arch and descending aorta (occurs in up to 25% of patients (Kasper 2015)
• Atresia of the pulmonalis (18 % - 22 % [Apitz 2005])
• Atrial septal defect (also called ASD V or Fallot Pentalogy; only rarely occurring - Apitz 2005) (Pinger 2019)
• valvular pulmonary stenosis (in 30 % to 76 %)
• missing pulmonary valve (at 1.6% - 4%)
• Peripheral pulmonary stenosis (at 20 % - 28 %)
• Hypoplasia of a (mostly left) pulmonary artery (in 22%)
• Aplasia of one (mostly the left) pulmonary artery (at 2%)
• Atrial septal defect (at approx. 1.5 % - 3.8 %)
• additionally existing muscular apical or inletventricular septal defect (in 5 %)
• presence of A. lusoria (at 1 % - 5 %)
• persistent left superior vena cava (at about 11%)

without information on frequency:

• persistent Ductus arteriosus, also called Ductus arteriosus apertus (corresponds to the so-called Fallot VI or Fallot- Hexalogy in case of a simultaneous atrial septal defect)
• supravalvular pulmonary stenosis
• Partially malfunctioning pulmonary veins
• Tricuspid valve anomalies
• Mitral valve anomalies
• Endocardial fibroelastosis (Apitz 2005)

Associated non-cardiac diseases:

Extracardiac abnormalities are also relatively frequent in the Fallot tetralogy. These include:

• malformations of the gastrointestinal tract
• Fissions
• in children with trisomy 18 and trisomy 21 this vitium occurs in about 10 % (Strauss 2008)
• Hyperuricemia (Stierle 2017)

It is a congenital malformation. It is caused by an inhibition of the correct rotation in the bulbotruncal region and a disturbed fusion with the endocardial cushion (Strauss 2008).

In about 9 % - 17 % of patients with uncomplicated tetralogy of Fallot, a microdeletion on chromosome 22q11.2 could be detected and in Fallot patients with a right aortic arch even in 60 % to 70 % (Weil 2011).

The clinical picture varies greatly depending on the extent of the ventricular septal defect and the severity of the pulmonary stenosis (Pinger 2019). In the presence of a higher degree of obstruction of the right-sided outflow tract, central cyanosis is present early on. If there is only a low degree of RVOTO, the acyanotic form, also called "pink Fallot" (Herold 2019), occurs, in which an almost asymptomatic course can persist into adulthood (Apitz 2005).

In about 45% of patients the first symptoms appear within the first 14 days postpartum and in about 80% within the first trimester of life. These are:

• Drinking difficulties
• Tachypnea
• Dyspnea
• hypoxemic attacks (these are caused by a narrowing of the hypertrophied infundibulum, which causes a blockage of the pulmonary circulation [Herold 2019]; they can occur from about the 3rd month of life [Briese 2010]) (Apitz 2005)

In the further course of the project, there will be more to come:

• missing weight gain up to dystrophy (Apitz 2005)
• Crouching position from infancy (this increases system resistance, leads to an increase in lung perfusion and thus to an increase in oxygen saturation [Herold 2019])
• visible cyanosis (found in approx. 25 % of newborns and in approx. 75 % of infants up to 12 months) (Apitz 2005)
• Vertigo with or without syncope
• epileptic attacks
• cerebral embolisms
• Brain abscess
• Thromboses (Stierle 2017)
• slight delay in development (Herold 2019).
• Endocarditis (Weil 2011)

Chest X-ray:

Although a chest x-ray is not essential for diagnosis, it should be performed preoperatively to identify or exclude extracardiac thoracic abnormalities and also as a basis for subsequent follow-up examinations (Weil 2011).
Radiographs can show:

• normal heart size
• hypertrophic right ventricle with raised and rounded cardiac apex (so-called wooden shoe heart or also called "coeur en sabot" [Pinger 2019])
• heart waist retracted (arises as a result of hyperplasia of the pulmonary artery)
• the central pulmonary vessels are hypoplastic (due to decreased pulmonary perfusion [Pinger 2019])
• the truncus pulmonalis is dilated
• the aorta is displaced to the right (Stierle 2017)
• partial lobular emphysema (may result from bronchus obstruction in the absence of a pulmonary valve [Apitz 2005])

Echocardiography

Echocardiography can usually be used to confirm the diagnosis of tetralogy of Fallot (Apitz 2005).

2- D- Echocardiography:

• the ventricular septal defect and the overriding aorta can be visualized parasternally in the long axis
• Pulmonary stenosis can be visualized parasternally in the short axis.

Note: Clear visualization of the ventricular septal defect, pulmonary stenosis, and aorta from subcostal is possible in neonates (Stierle 2017).

cw- Doppler:

• Determination of the pressure gradient across the RVOT.
• Detection of ventricular septal defect (Stierle 2017).

Color- Doppler:

• Obstruction of the RVOT
• Obstruction of the pulmonary valve
• Detection of ventricular septal defect (Stierle 2017).

Transesophageal Echocardiography (TEE):

TEE should be performed only if thoracic imaging is inadequate. This can be used to assess, among other things:

• Morphology of the RVOT
• Morphology of the pulmonary valve
• Positional relationship between the ascending aorta and the ventricular septal defect (Stierle 2017).

Cardiac MRI

Cardiac MRI is usually of no significance in preoperative diagnostics (Weil 2011).

In postoperative follow-up, however, this examination is used in cases of pulmonary valve regurgitation and to assess the size and function of the right ventricle (Stierle 2017).

Cardiac Catheterization

Cardiac catheterization is not generally required for the diagnosis of tetralogy of Fallot.

However, it may be indicated for:

• V. a. multifocal perfusion of the pulmonary arteries (through aortopulmonary collaterals).
• possibly also in case of echocardiographic evidence of anomaly of the coronary arteries (Weil 2011).

In infants, this examination should be performed early - if necessary - because hypoxic seizures can be triggered by the examination in the further course of Fallot tetralogy (Apitz 2005). During this examination, statements can be made about the:

• Anatomy of the heart
• anatomy of the pulmonary arteries
• the pressure and flow conditions can be quantified
• assessment of the coronaries (anomalies of the coronary vessels are found in about 30% [Stierle 2017])
• associating anomalies can be detected (Herold 2019)

Inspection and palpation

• central cyanosis (Stierle 2017)
• Clock glass nails (can form as early as 1 year of age)
• Drumstick fingers and toes (form no earlier than 2 years of age) (Apitz 2015)
• Voussure (forward hunching of the anterior thoracic wall [Pinger 2019])
• Systolic buzzing over the stenosis of the right ventricular outflow tract
• Precordial impulse over the lower third of the sternum (Stierle 2017).

Auscultation

• singular loud 2nd heart sound, only A2 is audible (arises from aortic valve closure)
• aortic ejection click (usually auscultable only after 20 years of age)
• systolic expulsion murmur in the 3rd ICR left parasternal over the RVOT (this is quieter the more severe the RVOT obstruction and may disappear completely during a hypoxic attack [Stierle 2017] )
• diastolic reflux murmur auscultable above the base of the heart in adults (arises from aortic valve regurgitation, less commonly from pulmonary valve calcification)
• in the presence of a ductus arteriosus apertus, a continuous murmur is found at the left upper sternal border (Apitz 2005 / Stierle 2017)
• to- and- fro- murmur with medium- to high-frequency diastolic component in the absence of a pulmonary valve (Apitz 2005).

ECG

An ECG should be derived preoperatively in any case as initial findings (Weil 2011). Typical findings are:

• Right atrial type (if left atrial type, AV canal malformation should be excluded [Stierle 2017]).
• right atrial hypertrophy signs (rarely occurring [Kasper 2015])
• Ventricular hypertrophy signs (these are rarely as pronounced as in tetralogy of Fallot [Stierle 2017]) such as:
  • Sokolow- Lyon index as a sign of right heart hypertrophy ( RV1 +SV5/6 > 1.05 mV)
• Incomplete right bundle branch block (Pinger 2019)
• extrasystoles (occur only after the age of 8 [Apitz 2005])

Pulse oximetry

Pulse oximetry should be used in all examinations, as it objectifies both the severity and progression of central cyanosis. If the transcutaneously measured O2- values indicate a saturation of < 80%, immediate action is required. (Weil 2011)

The differential diagnosis must be distinguished from a tetralogy of Fallot:

• Malalignment ventricular septal defect (here there is a ventricular septal defect with an overriding aorta, but without pulmonary stenosis)
• Pulmonary atresia with ventricular septal defect (in former times also called "extreme fallot")
• Truncus arteriosus communis (in this case a tetralogy of Fallot with pulmonary atresia must be excluded by differential diagnosis)
• double outlet right ventricle = DORV (comprises a heterogeneous group of heart malformations in which the aorta and pulmonary artery originate from the right ventricle, but without pulmonary atresia or stenosis [Koletzko 2004])
• Ventricular septal defect with discontinuity of the aortic and mitral valve (Strauss 2008)
• Transposition of the large arteries with ventricular septal defect and pulmonary valve stenosis
• corrected transposition of the large arteries with ventricular septum defect and pulmonary valve stenosis
• Single ventricle with pulmonary valve stenosis
• Endocardial cushion defect with pulmonary valve stenosis (Stierle 2017)
• Pulmonary valve agenesia, also called "absent pulmonary valve syndrome" (Weil 2011)

Conservative treatment options include:

• Endocarditis prophylaxis

This should be given to patients who have not previously had corrective surgery. Also for 6 months after corrective surgery and in patients who have had their pulmonary valve replaced surgically or interventrally (Weil 2011).

Therapy recommendation:

• administer antibiotic prophylaxis as a single dose 30-60 min before surgery;
• if oral administration is possible, amoxicillin or ampicillin 2 g p. o. can be administered
• if oral administration is not possible, ampicillin or cefalexin 2 g i.v. is recommended
• in case of ampicillin or penicillin allergy, clindamycin 600 mg should be given orally
• if i.v. administration is necessary, clindamycin 600 mg i.v. (Herold 2018).
• Iron substitution

Therapy recommendation: e.g. Eryfer 1 x 100 mg / d until the Hb- normal range is reached; regular checks of the blood count are necessary because of the risk of polycythemia under iron substitution.

• Beta-blocker as permanent medication for prophylaxis of hypoxemic seizures.

Therapy recommendation: see below "Therapy of hypoxemic seizures".

• Allopurinol in hyperuricemia; therapy recommendation: 100 - 300 mg /day
• in case of intercurrent diseases etc. fluid losses have to be compensated consequently
• if necessary, phlebotomy should be performed with regular monitoring of platelet function and PTT (Stierle 2017).

Palliative drug treatments that may be considered are:

• Prostaglandins

Continuous administration of prostaglandins until surgical intervention (if pulmonary hemorrhage is duct dependent [Weil 2011]). This is done by infusions of prostaglandin E1. Doses should be as low as possible (e.g., 5 - 10 ng/kg/min), otherwise the risk of side effects such as respiratory depression or circulatory depression increases. (Paul 2014)

• Beta- blocker: If transcutaneously measured oxygen saturation drops to < 85% due to increasing infundibular stenosis, propranolol (2 mg - 6 mg / kg/d) can be administered as a continuous infusion until the planned surgical procedure. Gradual dosing is required, especially in young infants. The target dose should be the highest tolerated dose. (Weil 2011)

Treatment of hypoxemic seizure

Treatment of hypoxemic seizure follows a stepwise regimen:

1. squatting position or simulation of squatting position (by holding the child on the arm and bending both knee joints).

2. sedation of the child, e.g. 5 mg - 10 mg diazepam as rectiole

3. oxygen administration via a nasal tube, e.g. 4l - 6l / min

4. administration of morphine if necessary, e.g. 0.01 mg - 0.1 mg /kg bw s.c.

5. volume administration i.v. to expand the intravascular volume

6. in case of persistent cyanosis and base deficit demonstrated by blood gas analysis, NaHCO3 should be administered up to 5 mmol/l

7. in case of pronounced hypotension, administration of a vasoconstrictor, e.g. dopamine in a low dose with bloody RR monitoring; however, there is a risk of intensification of the already existing RVOT obstruction

8. administration of beta-blockers, e.g. Dociton in small i.v. doses (0.025 mg - 0.1 mg/kg bw)

9. ultimately, only general anesthesia remains as the ultima ratio (Stierle 2017).

Contraindicated are:

• Digitalis glycosides
• arterial vasodilators
• ASS
• NSAIDs (Stierle 2017)

The basic goal of treatment in tetralogy of Fallot is to close the ventricular septal defect and to remove the obstruction of the right ventricular outflow tract.

However, the timing of corrective surgery is controversial. If there is marked cyanosis, the corrective procedure can be performed in the neonatal period. However, the European database (EACTS congenital database) as well as an American multicenter study indicate that early mortality is significantly increased with surgery in the neonatal period (10% vs. 1.6% or 7.8% vs. 0.9% in the multicenter study) (Weil 2011). A recent study by Ghimire (published in the American Journal of Cardiology on October 11, 2019) also confirmed this. It also showed even higher rates of complications, such as.

• Acute renal failure (8.9% vs. 2.3%)
• need for cardiac catheterization (18.6 % vs. 8.3 %)
• Need for ECMO (4.4 % vs. 1.6 %)

There were no other complications such as the occurrence of arrhythmias, respiratory arrest, sudden cardiac death, and pulmonary hypertension (Ghimire 2019). From there, if clinically justifiable, it is recommended that corrective surgery be performed electively between 4 and 12 months of age (Weil 2011).

Surgical options basically consist of surgical-palliative and surgical-corrective operations (Pinger 2019).

Surgical-palliative.

If primary corrective surgery is not possible (e.g., hypoplastic pulmonary arteries, hypoplastic valvular ring, coronary anomalies, multiple ventricular septal defects, etc.[Herold 2019]), palliative surgery to ensure adequate pulmonary perfusion must be performed for survival in cases of severely stenotic or functionally atretic RVOT (Weil 2011). This palliative surgery consists of an anastomosis between the systemic and pulmonary circulation, e.g., according to Pott, Waterston, or Blalock- Taussing (20- year survival in this case is approximately 55% [Strauss 2008]) (Pinger 2019)

Surgical-corrective

In surgical-corrective surgery, the obstruction of the

• the obstruction of the right ventricular outflow tract is removed by valvulotomy of the pulmonary valve and / or resection of the infundibular musculature
• patch dilatation by pericardial or plastic PTFE patch is often necessary
• closure of the atrial septal or ventricular septal defect is also required (Herold 2019).

Indications for corrective surgery: If anatomy permits, corrective surgery should be performed in all symptomatic cases (Stierle 2017).

Surgical lethality: Surgical lethality is < 5% (Stierle 2017). A differentiation is made between lethality in children, which is < 1%, and that in adults, which can be as high as 9%.

Re-operation: Within 20 years, approximately 10%-15% of patients require RE surgery (Pinger 2019). For the most part, these are pulmonary valve problems. This can be both insufficiency and stenosis of the valve, requiring surgical or interventional re- surgery (Kasper 2015).

Postoperative residual or sequelae:

• Ventricular arrhythmias: They occur in up to 50% of operated patients and can cause sudden cardiac death in about 6% of cases.

Risk factors for the arrhythmias may be:

• a QRS duration of > 180 msec
• inhomogeneous de- or repolarization
• abnormalities of the heart rate turbulence (HRT). The response of the heart rate to an extrasystole is quantified by the Turbulence Onset (TO) and the Turbulence Slope (TS) (Kovarovsky 2006).
• impaired left ventricular (!) function

Ventricular arrhythmias are responsible for approximately 30% to 50% of deaths in tetralogy of Fallot.

• supraventricular arrhythmias
• occurrence of an AV block of III degree
• Aneurysm of the RVOT (Stierle 2017).
• Risk of residual shunt in case of incomplete closure of the ventricular septum
• progressive dilatation of the right ventricle with systolic dysfunction (Pinger 2019)
• risk of endocarditis is relatively low after corrective surgery (Herold 2019)

The average life expectancy without surgical measures is about 12 years. Only about 10% of patients reach the age of 20 (Stierle 2017).

After surgical treatment, the survival rate is about 90% after 30 years and about 75% after 40 years (Herold 2019).

Spontaneous course: Due to the defect, fetal hemodynamics remain almost unaffected. Postpartum, the extent of vitium is dependent on the ductus arteriosus. As soon as this closes, cyanosis occurs (Strauss 2008). The extent of cyanosis determines the spontaneous course. The more pronounced the cyanosis, the shorter the natural course (Stierle 2017).

It is not uncommon for a natural course to result in the appearance of:

Polyglobulia

Iron deficiency

Endocarditis

cerebral abscesses

The incidence of this increases with age (Weil 2011).

Regular lifelong check-ups are usually required once a year (Weil 2011). Stierle (2017) generally recommends six-monthly check-ups because of the risk of post-operative complications, even after a successful curative operation.

The examinations should be carried out in EMAH centres (centre for adults with congenital heart defects) (Pinger 2019).

The controls should include the following examinations in particular:

• ECG with special focus on the QRS width (risk factors for arrhythmias are
  • Width increase of > 3,5 msec / year
  • or increase in width by > than 180 ms)
• Long term ECG

This should be done at least every 3 years because of the risk of arrhythmias in patients aged 10 years and older.

• Echocardiography
• MRI

MRI is particularly important in patients with significant pulmonary valve insufficiency and in patients with increasing enlargement of the right ventricle.

• Spirometry

A spirometric examination for objectification is therefore important, since patients usually do not subjectively notice a reduction in performance. The examination should be carried out at least every 5 years in children aged 10 years and older.

(Because 2011)

Genetic counselling

Since in the case of Fallot tetralogy there is sometimes a microdeletion on chromosome 22q11.2, genetic counselling is recommended if there are appropriate indications.

If a sibling is affected by the heart defect, the risk of recurrence is 2.5%. If 2 or more siblings are affected, the risk of recurrence is already 8% (Weil 2011).

If the mother has a tetralogy of Fallot, the risk of recurrence is 2.5% and if the father is affected, the risk of recurrence is 1.5%. (Strauss 2008).

Pregnancy: In any case, corrective surgery should have been performed prior to pregnancy (Briese 2010). There are considerable maternal and fetal risks in patients with arterial oxygen saturation of < 85 %. For this reason, these patients are generally advised against pregnancy (Rath 2005). The pregnancy should be closely monitored. From a cardiological point of view, delivery is to be preferred as a spontaneous vaginal delivery. In practice, however, a primary caesarean section is usually performed because of the planned intensive therapy. Epidural anaesthesia is controversially discussed.

Peripartal hypovolemia and a drop in blood pressure must be avoided at all costs. Oxytocin and ergometrin preparations are contraindicated post partum (Briese 2010).

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