Tetralogy of Fallot

Tetralogy of Fallot

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Tetralogy of Fallot (ToF) is defined by the following congenital heart abnormalities:

• Right ventricular outflow tract (RVOT) obstruction
• Ventricular septal defect (VSD)
• Overriding aorta
• Concentric right ventricular hypertrophy (RVH)

ToF is the most common congenital heart defect, with about 1 in every 2500 babies born in the US having the condition per CDC data. The exact embryological abnormality that causes ToF has not yet been elucidated, but it is associated with certain syndromes (e.g. Trisomy 21, DiGeorge syndrome, Alagille syndrome).

Anesthetic Implications

Preoperative Optimization

Preoperative optimization of a patient with ToF involves careful considerations of patient’s specific anatomy (see ‘Anatomy’ below) and extent of their disease. Namely, the following should be considered for the patient:

• The extent of decreased pulmonary blood flow
• Evidence/potential for hypercyanotic spells
• Other anatomy/physiology that may affect the patient’s management

Historically, management of ToF has been dependent on the degree of RVOT obstruction, which influences the amount of pulmonary blood flow. Echocardiography, EKG, chest radiograph, cardiac catheterization, CT, and MRI can all be used to map out the patient’s specific anatomy and guide surgical planning (see ‘Diagnosis’ below). Classically, infants with ToF are prone to “Tet spells,” or hypercyanotic episodes (see ‘Clinical Features’ below), in which there is acute desaturation and often clinical deterioration caused by reduction in pulmonary blood flow from right-to-left shunting. These episodes only occur in patients with ToF who have not had the defects surgically repaired and also have closed PDAs. There are many well-described triggers for these such episodes, many of which involve sympathetic stimulation (see ‘Clinical Features’ below). Taking a thorough history to find out what a patient’s history of hypercyanotic episodes and their triggers can guide preoperative management. In addition, when planning any surgical procedure for a patient with untreated ToF, it is key to take measures in order to avoid any hypercyanotic episodes during the procedure:

• Avoidance of excessive decreases in systemic vascular resistance (e.g. excessive use of vasodilatory drugs, prompt correction of hypotension)
• Avoidance of excessive increases in pulmonary vascular resistance (e.g. hypoxemia, acidosis)
• Avoidance of excessive sympathetic stimulation (having an age-appropriate pain regimen, anxiolysis if necessary)
• Avoidance of hypovolemia (minimization of the preoperative NPO period, ensuring good IV access)
• Management of arrythmias, should they occur

 In neonates born with a severe degree of RVOT obstruction or pulmonary atresia, it is likely that they will be medically managed with prostaglandin E1 (PGE1, alprostadil) to maintain a patent ductus arteriosus (PDA). PGE1 therapy is associated with several serious adverse effects, including apnea, hypotension, tachycardia, and necrotizing enterocolitis (thought to be more due to mesenteric hypoperfusion from maintenance of the PDA rather than a direct effect of PGE1). Finally, other causes of cyanosis, hypoxia, etc. should be ruled out.

Intraoperative Management

There are several factors to consider for intraoperative management of patients with ToF, regardless of the procedure being performed. Similarly to above, these are mostly geared at preventing any acute hypercyanotic episodes stemming from worsening right-to-left shunting, especially in patients with significant RVOT obstruction:

• Avoidance of excessive decreases in systemic vascular resistance (e.g. excessive use of vasodilatory drugs, prompt correction of hypotension)
• Avoidance of excessive increases in pulmonary vascular resistance (e.g. hypoxemia, acidosis)
• Avoidance of excessive sympathetic stimulation (e.g. pain)
• Avoidance of hypovolemia (early correction of fluid deficits)
• Avoidance of excessive increases in cardiac contractility or tachycardia
• Management of arrythmias, should they occur

In the literature, ketamine is preferred at induction of anesthesia because of its property of increasing SVR. Ketamine + fentanyl as well as ketamine + rocuronium have been described in case reports as standard approaches to induction.

Postoperative Management

There are several postoperative complications associated specifically with ToF repair:

• Residual anatomic lesions, including VSD, RVOT obstruction, and pulmonary regurgitation
• Arrhythmias (atrial, ventricular, junctional ectopic tachycardia)
• Restrictive right ventricular pathology and possible low cardiac output syndrome
• Pleural effusions

In addition, it is important to adhere to the same principles described above in terms of avoiding any potential triggers of a hypercyanotic episode, even in patients who have undergone repair for ToF.

Despite these possible complications, most children undergoing repair do well and are discharged within a week of surgery.

Anatomy/Pathophysiology

As mentioned above, the four heart abnormalities that classically comprise ToF are right ventricular outflow tract (RVOT) obstruction, ventricular septal defect (VSD), an overriding aorta, and right ventricular hypertrophy (RVH). It is thought that anterior and cephalad deviation of the infundibular septum during development is responsible for much of the anatomic defects that comprise ToF. Right Ventricular Outflow Tract Obstruction The location and degree of RVOT obstruction can be variable and at multiple levels (subvalvular, valvular, supravalvular). It is also possible for hypoplastic or stenotic branch pulmonary arteries to be present. More severe degrees of obstruction can lead to right-to-left shunting via the VSD, and thus cyanosis. On the other hand, mild or minimal RVOT obstruction will result in left-to-right shunting via the VSD, which can in turn result in increased pulmonary blood flow. Ventricular Septal Defect Most commonly, the VSD seen in patients with ToF is a single, large, nonrestrictive, subaortic, malaligned defect. It is usually contained within the perimembranous region of the septum but can rarely extend into the muscular septum.   Overriding AortaIn patients with ToF, the aorta is often displaced rightwards such that it lies over the misaligned VSD rather than the left ventricle. As a result, the aorta receives blood flow from both ventricles, rather than just the left. Right Ventricular Hypertrophy

In patients with ToF, minimal RVOT obstruction, and a large VSD, the left-to-right shunting that results leads to increased pulmonary blood flow as stated above. This can then result in pulmonary over-circulation, cyanosis, right ventricular hypertrophy, and eventually heart failure.

Other Variants

ToF with Pulmonary Atresia

In this variant of ToF, which is considered one of the most severe, there is complete atresia/occlusion of the pulmonary valve and thus no forward flow from the right ventricle into the pulmonary arteries. Intracardiac mixing of blood becomes essential for survival and is achieved via either a patent ductus arteriosus or major collateral arteries from the aorta to the pulmonary arteries (abbreviated as MAPCAs). ToF with Absent Pulmonary Valve In this variant, the patient has no pulmonary valve, but also no RVOT obstruction. Patients will often be acyanotic as a result, but their pulmonary arteries are prone to aneurysmal dilation due to the lack of pulmonary valve. In addition there will be pulmonary regurgitation. Consequently, compression of the airway (distal trachea, bronchi) is common and can result in obstructive pathology, atelectasis, and pulmonary hypoplasia. There are many other anatomic variants of ToF which are beyond the scope of this article.

Pathophysiology

Hypercyanotic Episodes ("Tet spells")

Classically, infants with ToF are prone to hypercyanotic episodes, or “Tet spells,” in which there is acute desaturation and often clinical deterioration caused by reduction in pulmonary blood flow from right-to-left shunting. These episodes only occur in patients with ToF who have not had the defects surgically repaired and also have closed PDAs. The pathophysiology of a hypercyanotic episode involves the following:

The right-to-left shunting that causes a hypercyanotic episode can have a wide variety of triggers. In theory, at baseline, the pressure in the two ventricles is equal due to the large and non-restrictive nature of the VSD in patients with ToF. Patients with more severe RVOT obstruction are at baseline more sensitive to acute right-to-left shunting, but any physiological change that leads to increased pulmonary vascular resistance (e.g. hypoxia), decreased systemic vascular resistance (e.g. sepsis, vasodilation, hot baths), or cardiac infundibular spasm (e.g. crying, pain, beta agonists) can increase such a shunt.

A right-to-left shunt will lead to hypoxia/increasing hypoxia as deoxygenated blood from the right heart is shunted to the left heart and then pumped into the systemic vasculature. Increased hypoxia leads to acidosis and an increased PaCO2, which in turn will lead to increased pulmonary vascular resistance. Increased pulmonary vascular resistance alone will lead to worsening of the right-to-left shunt as the right heart pumps even more blood across the VSD instead of into the increasingly resistant pulmonary vasculature. In addition, increased pulmonary vascular resistance triggers increased respiratory effort and tachypnea, which in turn will lead to increased systemic venous return. Systemic venous return, in turn, also worsens the right-to-left shunt. Thus, there is a vicious cycle that takes place in response to any trigger of a hypercyanotic episode, and can lead to acute desaturation and deterioration as stated above.

Chronic Hypoxemia

If left untreated, patients with ToF may suffer from chronic hypoxemia. This can lead to cyanosis as described above, but also secondary polycythemia, hypervisocisty of blood, and coagulation defects.

Clinical Features

Classically, patients with ToF present as neonates with mild-to-moderate cyanosis without respiratory distress (although respiratory distress is certainly possible depending on the extent of the anatomic defects). Pulse oximetry may show saturations between 75-80%, and the cyanosis will often fail to respond to oxygen therapy. It is possible for the cyanosis to come on gradually and worsen with age as well.

On physical exam, heart auscultation may reveal a pansystolic and/or ejection systolic murmur. The second heart sound may be single and loud. The flow of blood across the VSD in patients with ToF is usually not turbulent, and thus may not be heard; the murmur is more due to the RVOT obstruction. Interestingly, in a hypercyanotic episode, the blood flow across the obstructed RVOT tends to decrease, and thus a murmur that was previously present in a patient with ToF may disappear during such an episode. In addition, patients in a hypercyanotic episode will often become agitated and tachypneic. There are a wide variety of potential triggers for a hypercyanotic episode in patients with ToF. As described above (see 'Pathophysiology'), anything that decreases systemic vascular resistance, increases pulmonary vascular resistance, or increases sympathetic stimulation can trigger a hypercyanotic episode.

In addition, patients with ToF are prone to various arrythmias, with one study showing a 30% incidence of tachyarrythmia even in patients who had already undergone ToF repair.

Diagnosis

Some level of antenatal work-up and genetic analysis is possible in the diagnosis of ToF. As mentioned above, there are various syndromes associated with ToF, including but not limited to Trisomy 21, DiGeorge syndrome, and Alagille syndrome. ToF can be diagnosed in utero as early as 12 weeks of gestation via fetal echocardiography, although the mean gestational age is 20-21 weeks. Increasingly, routine fetal obstetric scanning is recognizing at least the suspicion for ToF. Echocardiography with Doppler is the widely accepted imaging modality for diagnosis of ToF, with transthoracic echocardiography usually being sufficient to obtain all necessary information. The location/number of VSDs, extent of RVOT obstruction, and any other structural defects can be seen/elucidated on echocardiography, and may prevent the need for other imaging. Other diagnostic modalities include EKG, chest radiograph, cardiac catheterization, high-resolution CT, and cardiac MRI. The following may be seen on these modalities in patients with ToF:

EKG: right atrial enlargement, right ventricular hypertrophy, and right axis deviation

Chest radiograph: may show the classic “boot-shaped” heart that results from an upturned cardiac apex due to right ventricular hypertrophy.

Cardiac catheterization: filling pressures usually normal or mildly elevated, LV and RV systolic pressures equal due to large VSD, pulmonary artery pressures usually normal or low. Right ventricle angiography can show the extent of RVOT obstruction and pulmonary artery anatomy.

High-resolution CT and cardiac MRI are much less commonly done, as they tend to carry higher radiation burden, or may require the patient to be anesthetized.

Treatment

For patients presenting with an acute hypercyanotic episode, management involves many of the principles detailed above (see 'Preoperative Optimization' and 'Intraoperative Management' above). Placement of the patient in a knee-chest position, administration of oxygen, IV fluid bolus with narcotic, beta blockade with propranolol or esmolol, and IV phenylephrine can be used in a stepwise fashion to resolve the episode. If all of the above fail, then acute intervention may be required.

Medical management of patients with ToF and severe RVOT obstruction involves infusion of prostaglandin E1 (PGE1), which maintains the patency of the ductus arteriosus (PDA) and thus allows for stable pulmonary blood flow.

Definitive treatment of ToF involves surgical repair, with most patients undergoing repair before one year of age or even before six months of age. A complete surgical repair is the treatment of choice, even in patients who are largely asymptomatic and acyanotic (i.e. the “pink variant” of ToF), as complete repair allows for normal growth of the RVOT and pulmonary annulus. Repair is generally deferred until three to four months of age in patients without severe RVOT obstruction and that can be medically managed. The complete surgical repair procedure consists of closure of the ventricular septal defect and enlargement of the RVOT. VSD closure is usually done via patch. Enlargement of the RVOT may entail relief of pulmonary stenosis/atresia, resection of infundibular muscle bundles, and/or a transannular patch between the right ventricle and main pulmonary artery. In patients with severe RVOT obstruction, severe hypercyanotic episodes refractory to medical treatment, preterm birth, or unusual anatomy that would complicate a complete repair, there are palliative interventions that can be done before the complete surgical repair. These palliative interventions are usually done in early infancy, and include the modified Blalock-Thomas-Taussig shunt (synthetic graft from innominate or subclavian artery to the pulmonary artery) and/or ductal/RVOT stenting.

Prognosis

In general, long-term prognosis of patients who have undergone ToF repair is excellent, with reports in the literature of survival rate at 20 years post-repair being ~85%. Some of the post-operative complications detailed above (see 'Postoperative management') have been shown to persist even long after repair, namely pulmonary regirgitation and/or stenosis and various arrythmias. For female patients with mild to minimal post-operative complications or residual cardiac pathology, pregnancy is judged to be low-risk. There is always the possibility that further interventions are indicated for cardiac repair, most commonly pulmonary valve replacements/repairs.

References

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