SECTION VIII - TETRALOGY OF FALLOT

Part I - Background Information

Definition

The defect is due to antero-cephalad deviation of the outlet septum resulting in: (1) an unrestricted large anterior malalignment subaortic VSD; (2) right ventricular outflow tract obstruction which may be infundibular, valvar, supravalvar or a combination of all; (3) consequent right ventricular hypertrophy; and (4) an overriding aorta (< 50%). Accompanying features can include additional muscular VSDs, anomalous coronary arteries, a right-sided aortic arch, PDA, aortic root dilation, and aortopulmonary collaterals (mainly seen in patients with pulmonary atresia/VSD, which is not discussed here).

The so-called pentalogy of Fallot also has an ASD or PFO.

 
Part II - Prevalence and Genetics

Approximately 15% of patients with tetralogy of Fallot have a deletion of chromosome 22q11 (97).The incidence is especially high in patients with right aortic arch, pulmonary atresia and aortic-to-pulmonary collaterals. The clinical spectrum is summarized in the 22q11 deletion syndrome (Cardiac defect, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia and 22q11 deletion). These patients may have an elevated risk of late psychiatric disorders. Deletion of 22q11 is usually sporadic. Affected subjects, however, have a 50% risk (autosomal dominant) of transmitting the deletion to their offspring.

 
Part III - History and Management of Unoperated Patients

The pathophysiology varies depending on the degree of right ventricular outflow obstruction.

With relatively mild obstruction, the presentation is of increased pulmonary blood flow and minimal cyanosis, so-called "pink tetralogy" or "acyanotic Fallot". This occasionally presents in adulthood.

Most children, however, have significant RVOT obstruction with consequent right-to-left shunt and cyanosis. Most of them will have had reparative surgery.

Rarely, adults present who are unoperated. For them, surgical repair is still recommended since the results are gratifying and the operative risk is comparable to pediatric series (provided there is good left ventricular function and no serious co-existing morbidity) (98,99).

Some patients reach adulthood with previous palliation only. The types of palliative procedures include:

• Blalock-Taussig shunt or modification (subclavian artery-to-pulmonary artery shunt).
• Waterston shunt (ascending aorta-to-right pulmonary artery).
• Potts shunt (descending aorta-to-left pulmonary artery).
• Central interposition tube graft.
• Infundibular resection (Brock procedure) or pulmonary valvotomy.
• RV-to-PA conduit without VSD closure or with fenestrated closure.

Reparative surgery involves closing the ventricular septal defect and relieving the RVOT obstruction. The latter may involve:

• Resection of infundibular muscle.
• Right ventricular subannular outflow tract patch.
• Transannular patch (a patch across the pulmonary valve annulus which disrupts the integrity of the pulmonary valve and causes substantial pulmonary regurgitation).
• An extracardiac conduit placed between the right ventricle and pulmonary artery (in cases of anomalous coronary artery crossing the RVOT).
• Replacement of the pulmonary valve.
• Pulmonary valvotomy
• Pulmonary arterioplasty.

A patent foramen ovale or secundum ASD should be closed and an AVSD repaired if present.

Additional lesions such as aortic regurgitation or muscular VSDs may also need to be addressed.

 
Part IV - Investigational Recommendations in Operated Patients

Investigations are directed toward the postoperative sequelae and will vary according to the type of operation performed.

All patients should have, at a minimum:

• A thorough clinical assessment.
• ECG.
• Chest x-ray.
• Echo Doppler examination by an appropriately trained individual to detect and quantify residual pulmonary stenosis and regurgitation, residual VSD, right and left ventricular size and function, aortic regurgitation, and aortic root size.

and may require:

• Exercise testing to assess functional capacity and to evaluate possible exertional arrhythmias.
• Holter monitoring.
• Quantitative lung perfusion scan in patients with suspected pulmonary artery branch stenosis.
• Heart catheterization if adequate assessment of the hemodynamics is not obtainable by non-invasive means, including pulmonary angiography in patients with suspected pulmonary artery branch stenosis and coronary angiography if surgical re-intervention is planned.
• EPS for those being evaluated because of sustained atrial flutter or fibrillation, or for sustained monomorphic ventricular tachycardia or fibrillation.
• MRI for the assessment of pulmonary artery or aortic anomalies, pulmonary regurgitant fraction as well as right ventricular size and function.

For those patients who have had previous palliation, assessment of pulmonary artery pressure and anatomy is mandatory at some point, since these shunts have inherent complications (distortion of the pulmonary arteries, stenosis or aneurysm in the shunt or at the site of anastomosis, development of pulmonary hypertension, and volume overloading of the left heart).

The following issues may need to be addressed following a palliative shunt:

• Determine whether complete repair is possible.
• Explain increasing cyanosis with erythrocytosis.
• Determine if pulmonary hypertension is present (unilateral or bilateral).
• Explain the reduction or absence of the continuous shunt murmur (suspected shunt stenosis or occlusion).
• Determine if there is aneurysm formation in the shunt.

Patients presenting as adults who have not been repaired may have elevated pulmonary artery pressures despite severe RVOT obstruction.

 
Part V - Indications for Re-intervention

Following palliative surgery, complete intracardiac repair should be considered in all patients, in the absence of severe irreversible pulmonary hypertension or unfavourable anatomy (inadequate pulmonary arteries). The following situations particularly warrant complete repair: Worsening symptoms. Increasing cyanosis with erythrocytosis. Reduction or absence of the continuous shunt murmur (suspected shunt stenosis or occlusion). Aneurysm formation in the shunt. Left ventricular dilation in the presence of aortic regurgitation or a left to right shunt.
Grade: Consensus		Ref: 99

Reoperation is only necessary in approximately 10-15% of patients following reparative surgery over a 20-year follow up.

The following situations may warrant intervention following repair: Residual VSD with a shunt > 1.5:1. Residual pulmonary stenosis with RV pressure 2/3 of systemic pressure (either the native RV outflow or valved conduit if one is present). Free pulmonary regurgitation associated with progressive or moderate to severe RV enlargement, important tricuspid regurgitation, sustained atrial or ventricular arrhythmias, or symptoms such as deteriorating exercise performance. Significant aortic regurgitation associated with symptoms and/or progressive left ventricular systolic dysfunction. Aortic root enlargement 55 mm in diameter. A large RV outflow tract aneurysm or evidence of infection or false aneurysm. Sustained clinical arrhythmias, most commonly either atrial flutter or fibrillation, or sustained monomorphic ventricular tachycardia. When any of these arrhythmias occur, a treatable cause of hemodynamic deterioration should be sought. The combination of residual VSD, and/or residual pulmonary stenosis and regurgitation, all mild-moderate but leading to progressive RV enlargement, reduced RV function or symptoms.
Grade: C	Level: V	Refs: 92,100-106

 
Part VI - Surgical/Interventional Options

Patients who require intervention should be operated on by congenital heart surgeons.
Grade: C	Level: V	Refs: 18,19

The following are possible intervention strategies:

• Surgery may be necessary for residual pulmonary stenosis; this may involve resection of residual infundibular stenosis or placement of an RV outflow or transannular patch. Occasionally a valved extracardiac conduit may be necessary.
• Aortic valve and/or root replacement may be necessary for those with aortic valve regurgitation and/or root dilation.
• Reoperation to insert a new pulmonary valve (either homograft or porcine) may be necessary for severe pulmonary regurgitation leading to right ventricular dilation, sustained arrhythmias and/or symptoms. Tricuspid valve annuloplasty may also be necessary when at least moderate tricuspid regurgitation is present.
• Suture or patch closure of a residual VSD if the shunt is 1.5:1 or if the patient is undergoing cardiac reoperation for other reasons.
• Branch pulmonary artery stenosis may be managed with balloon dilation stent insertion or surgery.
• Radiofrequency or surgical cryoablation for atrial flutter and sustained ventricular tachycardia. Maze procedure including pulmonary vein encirclement for atrial fibrillation.
• The role of AICD for arrhythmias in these patients is unclear.
• Closure of ASD or PFO, especially if there is persistent cyanosis or paradoxical embolus.

 
Part VII - Surgical/Interventional Outcomes

The overall survival of patients who have had operative repair is excellent, provided the VSD has been closed and the RVOT obstruction has been relieved. A 36-year survival of 85% has been reported (107). Death may occur from reoperation, endocarditis or congestive heart failure. The cumulative risk of sudden death following repair of tetralogy of Fallot seems to be about 1.2% at 10 years, 2.2% at 20 years, 4% at 25 year and 6% at 35 years (accounting for approximately one third of late deaths) (107,108).

Pulmonary valve replacement for chronic significant pulmonary regurgitation can be performed with a low mortality and may lead to improvement in right ventricular dimension and performance if performed before marked right ventricular dysfunction supervenes (106,109).

 
Part VIII - Arrhythmias

Whereas non-sustained ventricular arrhythmia on Holter is common, sustained monomorphic ventricular tachycardia is relatively uncommon. The latter relates to abnormal hemodynamics, usually from RV dilation secondary to pulmonary regurgitation and/or tricuspid regurgitation. QRS duration on the surface ECG correlates to RV size and when prolonged (QRS > 180 ms) is a sensitive (although less specific) predictor of sustained ventricular tachycardia and sudden death (110).

Restoration of hemodynamics through pulmonary valve implantation, tricuspid valve repair, or RVOT aneurysm resection, with concomitant intra-operative cryoablation has a positive effect on pre-existing sustained ventricular tachycardia (106,111). There is clearly a role for antiarrhythmic drugs, but addressing the underlying hemodynamics is usually the top priority. AICD implantation may also have a role for secondary prevention of sudden death; particularly so for patients with advanced ventricular dysfunction, non-responsive to re-operations or without hemodynamic abnormalities amenable to surgery.

Atrial flutter and fibrillation occur in one third of the adult patients and contribute to morbidity and even late mortality (112). As with sustained ventricular tachycardia, restoration of acceptable hemodynamics with concomitant cryoablation and antiarrhythmic medication are the main therapeutic tools (106,111).

 
Part IX - Pregnancy

Pregnancy in unoperated patients constitutes a considerable risk of maternal and fetal complications and death. This risk is greater when resting oxygen saturations are < 85%. The fall in peripheral resistance during pregnancy and hypotension during labour and delivery may increase the right to left shunt and aggravate pre-existing cyanosis.

The risk of pregnancy in repaired patients depends on the hemodynamic status. The risk is low, approaching that of the general population, in patients with good underlying hemodynamics. In patients with significant residual RVOT obstruction, severe pulmonary regurgitation with or without tricuspid regurgitation and RV dysfunction, the increased volume load of pregnancy may lead to right heart failure and arrhythmias.

All patients with tetralogy should have cardiology counseling pre-conception and follow up by an ACHD cardiologist during pregnancy. Pre-conception assessment of 22q11 deletion syndrome using fluorescent in situ hybridization (FISH) is recommended.

 
Part X - Follow-up

All tetralogy patients should have regular cardiology follow up by an ACHD cardiologist. Endocarditis prophylaxis is recommended.
Grade: Consensus