Tetralogy of Fallot With Pulmonary Stenosis

Tetralogy of Fallot (TOF) with pulmonary stenosis is the common form of tetralogy of Fallot, and it is the focus of this article.

Tetralogy of Fallot is a conotruncal defect resulting from anterior malalignment of the infundibular septum. This single morphologic defect gives rise to the 4 main components of Tetralogy of Fallot: (1) ventricular septal defect (VSD), (2) aortic valve overriding the ventricular septum, (3) narrowing of the right ventricular (RV) outflow tract (RVOT), and (4) RV hypertrophy (RVH).

A uniform etiology may explain this anatomic tetrad. That is, the monology of anterior deviation of the infundibular septum causes hypoplasia of the subpulmonary infundibulum and thus accounts for all components of the tetrad.

Tetralogy of Fallot is the most common cyanotic heart defect seen in children beyond infancy and occurs in 10% of all congenital defects. Furthermore, tetralogy of Fallot is the most common cyanotic congenital lesion that is likely to result in survival to adulthood. It is also the most common complex lesion to be encountered in the adult population after repair. Environmental associations with tetralogy of Fallot include maternal diabetes mellitus, retinoic acid exposure, and maternal phenylketonuria (PKU). This defect has a frequent association with the 22q11 chromosomal deletion and can also be seen associated with trisomy 21, 18, or 13. Other possible genetic associations are currently an ongoing area of active research.

Complex forms include tetralogy of Fallot with absent pulmonary valve and tetralogy of Fallot with pulmonary atresia with or without major aortopulmonary collateral arteries (MAPCAs).

See also Tetralogy of Fallot, Tetralogy of Fallot With Pulmonary Atresia, and Tetralogy of Fallot With Absent Pulmonary Valve.

Historical information

Tetralogy of Fallot holds a central place in the history of surgery for congenital heart disease; it was the first cyanotic cardiac lesion to be successfully managed with surgical palliation and was one of the first cardiac lesions to undergo successful intracardiac repair.

The classic Blalock-Taussig (BT) shunt procedure developed in 1945 involved direct end-to-end anastomosis between the subclavian artery and the pulmonary artery. This technique required transection of the subclavian artery. Professor Marc deLeval modified this procedure using an interposition conduit between subclavian artery and pulmonary artery. This modified BT shunt (also, deLeval shunt, Great Ormond Street [GOS] shunt), is currently the most commonly used systemic–to–pulmonary artery shunt.

Since the introduction of cardiopulmonary bypass, the trend has been for early and complete repair. The cardiopulmonary bypass machine is used to perform complete intracardiac repair of tetralogy of Fallot (see Corrective Surgery).

The following 4 diagnostic subgroups of tetralogy of Fallot (TOF) are described[1, 2] : (1) tetralogy of Fallot with absent pulmonary valve syndrome; (2) tetralogy of Fallot with common atrioventricular (AV) canal; (3) tetralogy of Fallot with pulmonary atresia; and (4) tetralogy of Fallot with pulmonary stenosis.

Tetralogy of Fallot with absent pulmonary valve syndrome

Tetralogy of Fallot with absent pulmonary valve syndrome is a form of tetralogy of Fallot with a severely dysplastic pulmonary valve and markedly dilated pulmonary arteries. This relatively rare lesion represents only 3-5% of all cases of tetralogy of Fallot. Tetralogy of Fallot with an absent pulmonary valve is commonly associated with respiratory difficulties. Severe problems with oxygenation—and especially ventilation—are thought to be related to bronchial compression secondary to the marked pulmonary artery dilatation.

Tetralogy of Fallot with common AV canal

Tetralogy of Fallot with common AV canal (AV septal defect [AVSD]) is the presence of both tetralogy of Fallot and complete AVSD. This rare lesion represents only 2% of all cases of Tetralogy of Fallot. Complete surgical repair of this lesion is riskier than repair of tetralogy of Fallot or AVSD alone. Nevertheless, combined complete repair is possible and usually successful.

Tetralogy of Fallot with pulmonary atresia

Tetralogy of Fallot with pulmonary atresia is a form of pulmonary atresia with ventricular septal defect (VSD) in which the intracardiac anatomy is tetralogy of Fallot. Tetralogy of Fallot with pulmonary atresia is commonly associated with hypoplastic branch pulmonary arteries and may be associated with major aortopulmonary collateral arteries (MAPCAs).

Tetralogy of Fallot with pulmonary stenosis

As noted in the introductory section, tetralogy of Fallot with pulmonary stenosis is the common form of tetralogy of Fallot. In this condition, pulmonary stenosis may be at the subvalvar, valvar, or supravalvar level, or it may involve any combination of these 3 levels.

The ventricular septal defect (VSD) in tetralogy of Fallot (TOF) is a perimembranous defect with extension into the subpulmonary region. Additional muscular VSDs may be present.

Right ventricular (RV) outflow tract obstruction (RVOTO) is present in the majority of cases of TOF, but it may be variable in severity. In addition to the subpulmonic obstruction, stenosis often coexists at the valvar and supravalvar levels. The pulmonary valve is atretic in the most severe form of the anomaly (15%). In some children, pulmonary atresia develops over time (tetralogy of Fallot with acquired pulmonary atresia).

The pulmonary annulus and main pulmonary artery are hypoplastic in most patients. The pulmonary artery branches are usually small, with variable peripheral stenosis. Narrowing at the origin of the left pulmonary artery is particularly common.

Systemic collateral arteries feeding into the lungs are occasionally present, especially in severe cases of tetralogy of Fallot such as tetralogy of Fallot with pulmonary atresia.

Other associated anomalies include a right aortic arch (present in 25% of patients); atrial septal defect (ASD), typically secundum ASD or patent foramen ovale; and patent ductus arteriosus (PDA).

Abnormal coronary arteries are present in about 5% of patients with tetralogy of Fallot. The most common abnormality is the left anterior descending (LAD) coronary artery arising from the right coronary artery (RCA) and passing over the RVOT. This coronary anomaly can necessitate modification of the surgical approach, because a transannular ventriculotomy may jeopardize the LAD that arises from the RCA.

The overall outcome after surgical repair of tetralogy of Fallot (TOF) has steadily improved since the technique was initially developed.[3] The continued improvement in outcome can be attributed to improved intraoperative technique, including the avoidance of excessive right ventricular (RV) outflow tract obstruction (RVOTO) muscle resection, improved cardiopulmonary bypass techniques (especially for infants), and improved postoperative care.

In the current era, survival to discharge after repair in most reported series is 95-99%, whereas in the early 1980s, the survival rate after TOF repair was approximately 90%. Thus, the current mortality risk for uncomplicated tetralogy of Fallot repair should approach 0%.

In a historical series, late survival was documented in 814 patients undergoing complete repair at the University of Alabama at Birmingham as 93% at 1 month and at 1 year, 92% at 5 years, and 87% at 20 years.[4] These survival rates were only slightly less than those of an age-matched, race-matched, and sex-matched control population. In the current era, late survival should even be better than it was in this series.

In the earliest days of surgical repair, postoperative complete heart block was a major problem. The rate of postoperative complete heart block decreased to 5% in earlier series and less than 1% in most recent series.

When the Society of Thoracic Surgeons Congenital Heart Surgery Database was used to analyze data from 941 patients undergoing TOF repair in 1998-2003, tetralogy of Fallot with pulmonary stenosis was present in 888 patients; tetralogy of Fallot with absent pulmonary valve syndrome was present in 34 patients; and tetralogy of Fallot with common atrioventricular canal (AVSD) was present in 19 patients.[5] The overall survival after discharge was 98.7%, with the highest risk among patients with TOF with absent pulmonary valve syndrome, who had a survival rate to discharge of only 91.2%. The incidence of insertion of a permanent pacemaker due to heart block was only 0.5%.[5]

Finally, in general, the prognosis for patients with TOF is excellent. In a study from the Society for Thoracic Surgery, patients undergoing repair of TOF between 2005-2009 at 74 centers had and an overall operative mortality rate of 1.1%, with many centers reporting no operative mortality.[6] A long-term follow-up study reported that among 1-year survivors after repair of TOF, actuarial 10-, 20-, 30-, and 36-year survival rates were 97%, 94%, 89%, and 85%, respectively.[7] In this group, patients without preoperative polycythemia and without an RV outflow patch had a 36-year actuarial survival rate of 96% and normal life expectancy.

Complications

Complications of the surgery for repair of TOF with pulmonary stenosis include the following:

• Hemorrhage

• Infection

• Heart block

• Residual or recurrent ventricular septal defect (VSD)

• Residual or recurrent RVOTO

• Pulmonary insufficiency

• RV dysfunction

• Heart failure

Patients requiring a pulmonary transannular patch develop progressive RV dilatation and are at higher risk of developing ventricular dysfunction and signs and symptoms of congestive heart failure.

Postoperative patients carry a lifelong risk of developing ventricular arrhythmias and sudden cardiac death. RV hypertrophy, ventricular dysfunction, residual RVOTO, prolonged QRS duration on ECG (>180 ms), and advancing age have all been reported to be predictors of ventricular arrhythmia and sudden death.[8, 9] Patients who do not receive a right ventriculotomy incision may be at lower risk of arrhythmia.[10]

In the current era, a large proportion of patients are diagnosed prenatally. Postnatally, the most common clinical presentation is an asymptomatic cardiac murmur. In early infancy, cyanosis may be mild or absent but tends to be progressive. Dyspnea upon exertion, squatting, or hypoxic spells may develop later.

Infants with acyanotic tetralogy of Fallot (pink tetralogy of Fallot) may be asymptomatic or may show signs of congestive heart failure (CHF) from a large left-to-right ventricular shunt.

Immediately after birth, severe cyanosis is seen in patients with tetralogy of Fallot and pulmonary atresia or severe pulmonary stenosis. These neonates may be ductal dependent and require urgent prostaglandin infusion to maintain ductal patency.

The natural history of untreated tetralogy of Fallot includes the following:

• The degree of cyanosis is related to the severity of right ventricular (RV) outflow tract obstruction (RVOTO)

• Infants with acyanotic tetralogy of Fallot gradually become cyanotic

• Patients who are already cyanotic become more cyanotic than before as a result of worsening infundibular stenosis and polycythemia

• Polycythemia develops secondary to cyanosis

• A relative state of iron deficiency (ie, hypochromia) may develop; patients require monitoring for this condition

• Hypoxic spells may develop in infants

• Growth retardation may be present if cyanosis is severe

• Brain abscess and stroke can occur but are rare

• Subacute bacterial endocarditis is occasionally a complication

• Aortic regurgitation may develop in some patients, particularly those with severe tetralogy of Fallot

• Coagulopathy is a late complication of a long-standing cyanosis

Varying degrees of cyanosis, tachypnea, and clubbing are present.

An increased right ventricular (RV) impulse along the left sternal border and a systolic thrill at the mid-left and upper-left sternal borders are commonly present.

An ejection click that originates in the aorta may be audible.

The S2 is usually single, because only the aortic component can be heard.

A long, loud (grade 3 to 5 or 6), ejection-type, systolic murmur is heard at the mid-left and upper-left sternal borders. This murmur originates from the pulmonary stenosis, but it may be easily confused with the holosystolic murmur of a ventricular septal defect (VSD). The more severe the RVOTO, the shorter and softer the systolic murmur.

In a neonate with tetralogy of Fallot, pulmonary atresia, and profound cyanosis, the heart murmur is either absent or soft, although a continuous murmur representing patent ductus arteriosus (PDA) may occasionally be audible.

In the acyanotic form, cyanosis is absent, and a long systolic murmur resulting from VSD and infundibular stenosis is audible along the entire left sternal border.

The diagnosis of tetralogy of Fallot (TOF) with pulmonary stenosis may be established with fetal ultrasonography. Until the early to mid 1990s, the overwhelming majority of patients with tetralogy of Fallot underwent diagnostic cardiac catheterization before surgical repair. Since the mid 1990s, most centers have surgically repaired the majority of patients with tetralogy of Fallot with preoperative echocardiography without preoperative cardiac catheterization.

Routine blood studies indicated in patients with tetralogy of Fallot with pulmonary stenosis include a complete blood cell (CBC) count, chemistry panel, and coagulation studies, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count.

The radiographic appearance of tetralogy of Fallot (TOF) varies with whether the condition is cyanotic or acyanotic.

Cyanotic tetralogy of Fallot

The cardiac size appears normal or smaller than normal, and pulmonary vascular markings are decreased.

In tetralogy of Fallot with pulmonary atresia, black lung fields are seen.

A concave main pulmonary artery segment with an upturned cardiac apex (ie, coeur en sabot [boot-shaped heart]) is characteristic.

Right atrial enlargement (25%) and a right aortic arch (25%) may be present.

Acyanotic tetralogy of Fallot

Radiographic findings of acyanotic tetralogy of Fallot are indistinguishable from those in a small to moderate ventricular septal defect (VSD), but patients with tetralogy of Fallot have right ventricular hypertrophy (RVH) rather than left ventricular hypertrophy (LVH) on the electrocardiogram (ECG).

On electrocardiogram (ECG), right axis deviation +120 to ±150° is present in cyanotic tetralogy of Fallot (TOF). In the acyanotic form, the QRS axis is normal.

On ECG, right ventricular hypertrophy (RVH) is usually present, but the strain pattern is unusual. Combined ventricular hypertrophy (CVH) may be seen in the acyanotic form. Right atrial hypertrophy (RAH) is occasionally present.

Two-dimensional (2-D) echocardiography and Doppler ultrasonographic studies are the diagnostic modalities of choice for Tetralogy of Fallot (TOF). Echocardiographic results confirm the diagnosis and help in quantitating the severity of tetralogy of Fallot.

A large, perimembranous, infundibular ventricular septal defect (VSD) and overriding of the aorta are depicted in the parasternal long-axis view.

The anatomy of the right ventricular (RV) outflow tract (RVOT), the pulmonary valve, the pulmonary annulus, and the main pulmonary artery and its branches is depicted in the parasternal short-axis view.

Doppler studies are helpful to estimate the pressure gradient across the obstruction in the RVOT.

Associated anomalies, such as atrial septal defect (ASD) and persistence of the left superior vena cava (SVC), can be imaged, and anomalous coronary artery distribution can be accurately assessed with echocardiographic studies.

Perioperative echocardiographic studies

Echocardiography is the diagnostic modality of choice for the preoperative evaluation of patients with tetralogy of Fallot. This technique is also the diagnostic modality of choice for the postoperative follow-up evaluation of patients with both palliated and repaired tetralogy of Fallot.

Transesophageal echocardiography (TEE) is used in the operating room to plan the repair and to assess the success of the repair.

Preoperative versus postoperative findings

Before surgery, tetralogy of Fallot represents a broad spectrum of VSD sizes and RVOT obstructions (RVOTOs). After surgery, residual abnormalities range from a nearly normal-appearing heart to one with substantial RV dysfunction and residual RVOTO. 2-D echocardiography and Doppler ultrasonographic techniques can be definitive means for monitoring patients with respect to their recovery of RV function and complications, such as recurrent RVOTO and residual or recurrent VSD.

In the modern era, preoperative cardiac catheterization is reserved for certain high-risk patients with tetralogy of Fallot (TOF).

In patients with tetralogy of Fallot with pulmonary atresia, cardiac catheterization is used to assess the anatomy, size, and distribution of the peripheral pulmonary artery. The presence, origin, and insertion of major aortopulmonary collateral arteries (MAPCAs) should be documented.

In preoperative patients before complete repair status but after previous systemic-to-pulmonary artery shunting, cardiac catheterization allows visualization of the shunt and the pulmonary artery at the shunt insertion site.

Preoperative cardiac catheterization solely for the assessment of coronary artery anatomy is not necessary, because these data can typically be obtained with echocardiography.

The prognosis of patients with unrepaired tetralogy of Fallot (TOF) is inferior to the life expectancy of those undergoing repair. Therefore, whether to repair tetralogy of Fallot is not often debated.

The timing of surgery and the initial surgical procedure performed in the patient with symptomatic tetralogy of Fallot remain controversial. The nature of the right ventricular (RV) outflow tract obstruction (RVOTO) often dictates the symptoms. In cyanotic tetralogy of Fallot, hypercyanotic episodes (tetralogy of Fallot spells) may occur with agitation or irritability. If the episode is profound, the child develops severe cyanosis, often with hypotension, hemodynamic instability, and altered consciousness.

Medical management of tetralogy of Fallot spells often includes use of mechanical ventilation, inotropes, and an alpha-agonist such as phenylephrine hydrochloride (Neo-Synephrine) to increase pulmonary blood flow. In neonates with spells, prostaglandins may be used to reestablish ductal patency; however, this approach is not always successful.

Patients whose condition is refractory to medical management and stabilization require urgent surgical intervention. In some centers, these patients are treated with initial surgical palliation with a systemic-to-pulmonary artery shunt and subsequent complete repair, whereas, in other centers, these children are treated with urgent primary complete repair.

Controversy also surrounds the timing of surgery in children with asymptomatic tetralogy of Fallot. In asymptomatic patients, some centers advocate that elective repair be performed from the neonatal period, whereas other centers wait until age 1 year. Most surgeons repair the infant with asymptomatic tetralogy of Fallot between ages 4 and 6 months.

In cyanotic patients with tetralogy of Fallot (TOF), conservative management includes the following:

• Knee-to-chest positioning

• Administration of supplemental oxygen

• Sedation

• Volume expansion

• Correction of anemia, if present

• Additional measures that increase cardiac preload and systemic vascular resistance

• Beta-blockade to decrease infundibular spasm

In acyanotic patients, medical management is similar to management of a patient with a ventricular septal defect (VSD) and may include diuretics (furosemide [Lasix]), digoxin, and afterload reduction (captopril).

The role of transcatheter interventions for tetralogy of Fallot (TOF) is controversial. Most centers do not use transcatheter interventions for tetralogy of Fallot and instead perform surgical palliation and repair.

Some centers advocate balloon dilation of the right ventricular outflow tract (RVOT) for infundibular and pulmonary valvar stenosis. The balloon dilation for pulmonary valvar stenosis is more likely to be successful than dilation for infundibular stenosis.

Patients who undergo transcatheter balloon dilation for recurrent RVOT after valve-sparing repair of tetralogy of Fallot appear to demonstrate acute reduction in the RVOT gradient, with more favorable outcomes in those with stenosis solely at the level of the valve.[11] However, balloon dilation often leads to an increase in pulmonary regurgitation and has a high rate of reintervention.

Cutting-balloon angioplasty of pulmonary artery stenosis in tetralogy of Fallot has been investigated but is not commonly performed. In certain high-risk infants, stenting of the RVOT has been performed. Elective surgical repair and stent removal can be performed later without longer cardiopulmonary bypass times or recognizable complications compared with shunted patients.[12, 13]

Transcatheter interventions do play a major role in the rehabilitation of the distal pulmonary arteries in the setting of tetralogy of Fallot with pulmonary atresia.

A systemic-to-pulmonary artery shunt is indicated in patients in whom the risk in complete repair is considered to be higher than the cumulative risk in 2-stage repair.

The timing and type of surgical intervention in tetralogy of Fallot (TOF) is controversial. In asymptomatic patients, elective repair has been advocated from the neonatal period up until age 1 year. Most surgeons perform repair in infants with asymptomatic tetralogy of Fallot between ages 4 and 6 months. In symptomatic or cyanotic patients, depending on institutional preferences, complete repair can be performed as a primary single-stage procedure or as a 2-stage approach, with initial systemic-to–pulmonary artery shunting.

The preoperative evaluation for tetralogy of Fallot (TOF) repair includes an assessment of functional status and pulmonary evaluation. Chest radiographic findings may depict the classic boot-shaped heart. Echocardiography is diagnostic, and associated anomalies can be excluded. Cardiac catheterization is indicated before repair of tetralogy of Fallot in patients with previous palliation and when aortopulmonary collaterals and pulmonary artery branching abnormalities are suspected (see Workup).

Preoperative diagnostic studies must provide the surgeon with the following data:

• The number, size, and location of all ventricular septal defects (VSDs)

• The severity and location of right ventricular (RV) outflow tract (RVOT) obstructions (RVOTOs)

• The size and distribution of the pulmonary artery

• The origins and branching pattern of the coronary arteries

• The origin and distribution of all sources of pulmonary blood flow, including major aortopulmonary collateral arteries (MAPCAs)

The role of palliative surgery for tetralogy of Fallot (TOF) is controversial. Patients whose conditions are refractory to medical management and stabilization require urgent surgical intervention. In some centers, these patients are treated with initial surgical palliation with a systemic-to–pulmonary artery shunt and subsequent complete repair. In other centers, these children are treated with urgent primary complete repair.[14, 15]

Creation of a systemic-to–pulmonary artery shunt can be performed from the midline by means of a sternotomy or thoracotomy. Advantages of the sternotomy approach include the simple use of cardiopulmonary bypass if necessary. Advantages of the thoracotomy approach include the preservation of a virgin sternotomy approach with a simplified sternotomy for the eventual complete repair with minimal adhesions.

A modified Blalock-Taussig (BT) shunt procedure is most commonly performed by using a polytetrafluoroethylene (Gore-Tex) tube graft anastomosed end-to-side to the right subclavian artery and end-to-side to the right pulmonary artery. The modified BT shunt is most commonly created on the side opposite the aortic arch. Therefore, with a left aortic arch, a right modified BT shunt is typically created. With a right aortic arch, a left modified BT shunt is typically created.

Complete intracardiac repair of tetralogy of Fallot (TOF) can be performed as a single-stage procedure or as a 2-stage approach, with initial systemic-to–pulmonary artery shunting.

Complete surgical repair involves closure of the ventricular septal defect (VSD) and relief of the right ventricular (RV) outflow tract obstruction (RVOTO). A median sternotomy approach is used with cardiopulmonary bypass.

Complete surgical repair goals

The goals of complete repair are relief of all obstruction to blood flow from the RV to the pulmonary artery and closure of the VSD. The relief of RVOTO may involve resection of obstructing RVOT muscle bundles, creation of an RVOT patch, creation of a transannular RVOT patch, pulmonary valvotomy or valvectomy, and pulmonary arterioplasty of the main and branch pulmonary arteries.[3] The VSD is usually closed with a patch taking great care to avoid damage to the conduction system.

Transventricular vs transatrial approach

Two potential surgical approaches are the transventricular approach and the transatrial approach. Transventricular repair with a right ventriculotomy in the infundibulum allows for exposure of the VSD and patch closure of the infundibular incision. With the transatrial approach, the VSD and subpulmonary obstruction can be approached from a transatrial direction. Muscle resection is performed to relieve the RVOTO.

Transannular patching

Assessment of the pulmonary annulus using predicted mean-normal diameters of the pulmonary valve annulus corrected for body surface area provides some guidance for enlarging the pulmonary annulus (transannular patching). A conduit connection from the RV to the pulmonary arteries may be necessary in patients with pulmonary atresia, anomalies of the coronary arteries, or severe multilevel obstruction and hypoplasia. Distal pulmonary arteries and branch pulmonary artery stenosis can be managed at the time of surgery by using autologous pericardial patch enlargement. Additional work on the branch pulmonary arteries can be accomplished preoperatively and postoperatively by means of the transcatheter approach.

In neonates and young infants, use of a transannular patch is most likely, and extensive RVOT muscle resection is not usually necessary. In select patients, intraoperative pulmonary balloon valvuloplasty can be used as an adjunctive therapy to relieve obstruction while preserving pulmonary valve integrity and function.[13] In older children, use of a transannular patch is relatively unlikely, and extensive RVOT muscle resection is common.

After surgery, various residual abnormalities may be encountered, ranging from a nearly normal-appearing heart to one in which substantial right ventricular (RV) dysfunction and residual RV outflow tract obstruction (RVOTO).[16]

Two-dimensional (2-D) echocardiography and Doppler ultrasonographic techniques can be the definitive means for monitoring patients with respect to the recovery of RV function and the development of complications, such as recurrent RVOTO and residual or recurrent ventricular septal defect (VSD) (see Workup).

Postoperative pulmonary insufficiency can be associated with late RV dysfunction and may necessitate intervention.

Clinical, electrocardiographic (ECG), and echocardiographic follow-up monitoring is indicated. Echocardiography is the diagnostic modality of choice for follow-up.

Further in/outpatient care

Some children, especially those repaired at a younger age, may require prolonged hospitalization. Causes are multifactorial but may include sepsis, residual left-to-right shunts through ventricular septal defects (VSDs), low cardiac output syndrome, ventricular dysfunction, or cardiac arrhythmias. Associated noncardiac problems, including feeding difficulties, renal insufficiency, or pulmonary insufficiency, may require ongoing management and delayed discharge.

Patients who are status post repair of tetralogy of Fallot deserve lifelong outpatient follow-up with a focus on early detection of signs of congestive heart failure or functional impairment, as well as ongoing surveillance for cardiac arrhythmias.

Two areas of controversy are briefly discussed in this section: the differentiation between tetralogy of Fallot (TOF) and double-outlet right ventricle (DORV) and the management of late pulmonary insufficiency.

Tetralogy of Fallot versus double-outlet right ventricle

The tetralogy of Fallot manuscript of The International Congenital Heart Surgery Nomenclature and Database Project clearly stated that the distinction between tetralogy of Fallot and DORV is controversial.[17] Some authors use the term DORV when the pulmonary artery arises from the right ventricle (RV) and when more than 50% of the aorta arises from the RV. Other authors use this term only when the pulmonary artery arises from the RV and when 90% or more of the aorta arises from the RV. Still others use the term only when fibrous continuity is absent between the aortic and mitral valves.

In the DORV manuscript of The International Congenital Heart Surgery Nomenclature and Database Project, DORV is defined as a type of ventriculoarterial connection in which both great vessels arise predominantly from the RV.[18] In the tetralogy of Fallot manuscript of The International Congenital Heart Surgery Nomenclature and Database Project, Marshall Jacobs stated, "It is inescapable that some hearts will be called tetralogy of Fallot at some centers and DORV at other centers."

Management of late pulmonary insufficiency

After repair of tetralogy of Fallot, many patients present in need of reoperative surgical reconstruction of the RV outflow tract (RVOT). The predominant physiologic lesion is often pulmonary insufficiency, but varying degrees of RVOT may also be present. In the past, patients were thought to tolerate pulmonary insufficiency reasonably well. However, in some, the long-term effects of pulmonary insufficiency and subsequent RV dilatation and dysfunction are associated with poor exercise tolerance and increased incidences of arrhythmias and sudden death.

Pulmonary valve insertion or replacement can be performed as treatment for pulmonary insufficiency to improve performance status, optimize hemodynamics, and improve control of arrhythmias. Indications for RVOT reconstruction in this setting and the surgical strategy continue to evolve. Several surgical options for pulmonary valve replacement are available, including the use of aortic and pulmonary homografts, stented and stentless porcine valves, porcine valve conduits, bovine jugular vein conduits, man-made polytetrafluoroethylene pulmonary valves, and even mechanical valves and mechanical valve conduits.

Over the last several years, concerns regarding postoperative pulmonary insufficiency or combined insufficiency and stenosis have increasingly emerged. The belief about patients' tolerance of pulmonary insufficiency after valvectomy and/or transannular patching during repair of tetralogy of Fallot is no longer simply accepted. The sequence of pulmonary insufficiency that causes volume overload leading to RV dilatation and dysfunction has been demonstrated with echocardiography and magnetic resonance imaging (MRI).[19, 20] Exertional symptoms often follow these objective changes in ventricular function and size and can be documented with exercise testing.

Further, peak oxygen consumption (VO2), ventilation-carbon dioxide (VE/CO2) slope, and heart rate reserve during exercise testing prediction have been shown to be predictive of early mortality.[21] Finally, life-threatening ventricular arrhythmias seem to be associated with relatively severe cases of pulmonary insufficiency and ventricular changes.

RV dilatation and dysfunction are reversible after pulmonary valve replacement. Therefore, as the population of children with repaired congenital heart disease ages, an increasing number of patients will benefit from pulmonary valve insertion. However, data suggest a lack of notable recovery of RV indices after pulmonary valve replacement in adults with long-standing pulmonary insufficiency. Therefore, the timing of pulmonary valve replacement is of major importance in the overall maintenance of ventricular function and optimal long-term outcomes. In addition, a program of aggressive pulmonary valve replacement in conjunction with intraoperative cryoablation is effective in decreasing QRS duration and in controlling ventricular arrhythmias in patients with tetralogy of Fallot and severe pulmonary insufficiency.

In general, indications for pulmonary valve replacement are evolving but currently include patients with moderate to severe pulmonary insufficiency and/or stenosis and any of the following: exertional symptoms of New York Heart Association (NYHA) class II or worse, RV dysfunction (RV ejection fraction <47%<ref>22</ref>, RV dilatation (RV end-diastolic volume index >150mL/m2 or Z score >4[22] ), decreased performance capacity on exercise testing, ventricular arrhythmias, and/or QRS duration of more than 160 ms.

The majority of patients with tetralogy of Fallot (TOF) require no medical therapy prior to undergoing surgical repair. In rare instances, medications may be needed to treat ductal patency in severely cyanotic neonates and signs of congestive heart failure in patients with a minimal degree of right ventricular outflow tract obstruction.

Hypercyanotic spells are initially treated with nonpharmacologic means, including knee-chest position, supplemental oxygen, and volume expansion. In more severe episodes, additional pharmacologic interventions may include beta-blocker therapy to reduce right ventricular infundibular spasm and alpha-1 agonists to increase systemic vascular resistance.

In/outpatient medications

Most patients are on no medications prior to surgical repair. Beyond the initial postoperative period, most patients are also are on no medications. Select patients may require medication to treat ventricular dysfunction, congestive heart failure, or cardiac arrhythmias.

Class Summary

The use of a vasodilator will reduce systemic vascular resistance, allowing more forward flow, improving cardiac output.

Alprostadil (Prostin VR Pediatric)

Severely cyanotic neonates may require prostaglandin E1 to maintain ductal patency in order to provide adequate pulmonary blood flow.

Intravenous prostaglandin E1 may be continued until the time of surgical palliation.

Class Summary

Loop diuretics decrease plasma volume and edema by causing diuresis. The reduction in plasma volume and stroke volume associated with diuresis decreases cardiac output and, consequently, blood pressure.

Furosemide (Lasix)

Patients with a minimal degree of right ventricular outflow tract obstruction may show signs and symptoms of pulmonary overcirculation. In these patients, diuretic therapy can be initiated to treat signs of congestive heart failure.

Class Summary

These agents improve the hemodynamic status by increasing myocardial contractility and heart rate, resulting in increased cardiac output. They also increase peripheral resistance by causing vasoconstriction. Increased cardiac output and increased peripheral resistance lead to increased blood pressure.

Phenylephrine

Phenylephrine is used to increase systemic vascular resistance.

Class Summary

These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.

Metoprolol (Lopressor, Toprol XL)

Beta-blocker therapy is used to reduce right ventricular infundibular spasm.

Hypercyanotic spells are initially treated with nonpharmacologic means, including knee-chest position, supplemental oxygen, and volume expansion. In more severe episodes, additional pharmacologic interventions may include beta-blocker therapy to reduce right ventricular infundibular spasm and phenylephrine to increase systemic vascular resistance.