Tetralogy of Fallot (TOF): Management and outcome

INTRODUCTION — Tetralogy of Fallot (TOF) includes the following major features (figure 1):

●Right ventricular (RV) outflow tract obstruction

●Ventricular septal defect (VSD)

●Deviation of the origin of the aorta to the right so that it overrides the VSD

●Concentric RV hypertrophy

TOF accounts for approximately 7 to 10 percent of all cases of congenital heart disease and is one of the most common cyanotic congenital heart defects. Morbidity and mortality of TOF have declined markedly with comprehensive management of these patients that includes initial medical care, surgical repair, and postoperative management of complications.

The management and outcome of TOF are discussed here. Other related topics include:

●(See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)

●(See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair".)

●(See "Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCAs)".)

INITIAL MEDICAL MANAGEMENT — The need for medical intervention is dependent on the degree of right ventricular outflow tract (RVOT) obstruction. Patients with severe obstruction have inadequate pulmonary flow and typically present in the immediate newborn period with profound cyanosis. These patients may need urgent therapy. Patients with moderate obstruction and balanced pulmonary and systemic flow usually come to clinical attention during elective evaluation for a murmur. These children may also present with hypercyanotic ("tet") spells when RVOT is obstructed during periods of agitation. Patients with minimal obstruction may present with increased pulmonary blood flow and heart failure. In addition, some affected newborns will be detected by an evaluation prompted by a failed oximetry screening test. (See "Newborn screening for critical congenital heart disease using pulse oximetry".)

Neonates with severe RVOT obstruction — Neonates with severe RVOT obstruction present with profound hypoxemia and cyanosis. These patients may require intravenous prostaglandin therapy (alprostadil) to maintain ductal patency and pulmonary flow pending surgical or catheter-based intervention [1]. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1'.)

Neonates with ductal dependency may require early palliative intervention (eg, palliative shunt placement, RVOT stent, or ductal stenting) before undergoing complete repair. (See 'Palliative intervention' below.)

Tet spells — Hypercyanotic (or "tet") spells present as periods of profound cyanosis that occur because of episodes of dynamic severe RVOT obstruction. They typically arise when an infant becomes agitated or in older, uncorrected children after vigorous exercise.

Management of hypercyanotic "tet" spells requires a rapid and aggressive stepwise approach:

●Place the patient in a knee-chest position.

●Administer oxygen.

●If these fail, administer an intravenous (IV) fluid bolus (normal saline 10 to 20 mL/kg) and a dose of narcotic. We typically use IV morphine (0.1 mg/kg per dose) for this purpose; intranasal fentanyl or midazolam have also been described as successful interventions in patients with difficult IV access [2,3].

●If the above measures fail, administer an IV beta blocker (eg, propranolol 0.1 mg/kg per dose or esmolol 0.1 mg/kg per dose). If single doses are ineffective, a continuous IV infusion of esmolol (50 to 75 mcg/kg/min) can be provided.

●If beta blocker therapy is insufficient, administer IV phenylephrine (bolus dose of 5 to 20 mcg/kg per dose, followed by continuous infusion).

●If all of these measures fail, extracorporeal membrane oxygenation support (ECMO), emergency complete surgical repair, or an emergency aorticopulmonary shunt is necessary.

These interventions work via the following mechanisms:

●The knee-chest position increases systemic vascular resistance (SVR), which promotes movement of blood from the right ventricular (RV) into the pulmonary circulation rather than the aorta.

●Oxygen is a pulmonary vasodilator and a systemic vasoconstrictor.

●The mechanism of action of morphine is unclear.

●Fluids improve RV filling and pulmonary flow.

●The presumed mechanism of beta blocker therapy is relaxation of the RVOT with improved pulmonary blood flow.

●Phenylephrine increases systemic afterload which promotes RV flow into the pulmonary circulation rather than the aorta.

Heart failure — Patients with minimal obstruction and increased pulmonary blood flow may develop heart failure symptoms from pulmonary overcirculation. Such patients may require pharmacologic treatment (eg, with furosemide and digoxin). (See "Heart failure in children: Management", section on 'Pharmacologic therapy'.)

Though commonly used in other types of heart failure, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are generally not used in patients with heart failure due to TOF because they can decrease SVR and may promote hypercyanotic ("tet") spells. (See 'Tet spells' above.)

Endocarditis prophylaxis — Patients with unrepaired or palliated TOF (eg, with a shunt or stent) may require antibiotic prophylaxis if they undergo certain dental, oral, or other invasive airway procedures (eg, tonsillectomy, cleft lip or palate repair) to reduce the risk of infective endocarditis. These procedures are uncommon in infants with unrepaired TOF since elective surgeries are typically deferred until after surgical repair. Nevertheless, if the infant does undergo one of these procedures, it is important to ensure that appropriate prophylactic antibiotics are administered, as summarized in the figure (algorithm 1) and discussed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

SURGICAL REPAIR — Most patients with TOF undergo complete repair as their initial intervention by one year of age (typically before six months of age) [4]. (See 'Complete repair' below.)

A small minority of infants require palliative shunts, right ventricular outflow tract (RVOT) stents, or ductal stents prior to surgical repair. Shunts or stents may be necessary due to severe RVOT obstruction or, less commonly, medically refractory hypercyanotic ("tet") spells. Shunts or stents may also be used in infants who are not initially acceptable candidates for intracardiac repair due to small size (eg, preterm infants), hypoplastic pulmonary arteries (PAs), or coronary artery anatomy. (See 'Palliative intervention' below.)

Complete repair — Primary intracardiac repair is the treatment of choice for most patients with TOF [4,5]. This includes asymptomatic acyanotic infants (pink variant) since surgical correction allows normal growth of the RVOT and pulmonary annulus [6].

Surgical procedure — The goals of surgical repair are:

●Relieve RVOT obstruction

●Separate the pulmonary and systemic circulations

●Preserve right ventricular (RV) function

●Minimize postprocedure pulmonary valvular incompetence

The surgery consists of patch closure of the ventricular septal defect (VSD) and enlargement of the RVOT, thereby relieving obstructed pulmonary flow. RVOT enlargement is accomplished by relieving pulmonary stenosis, resecting infundibular and sub-infundibular muscle bundles, and, if necessary, by a transannular patch, creating unobstructed flow from RV into the PAs (figure 2).

When feasible, a transatrial approach is utilized to access the RVOT and close the VSD in an effort to avoid ventriculotomy, which carries a risk for late ventricular arrhythmias. This approach is most likely to be successful in patients with discrete infundibular stenosis and an adequate pulmonary annulus [7].

Increasingly, surgical approaches emphasize maintaining pulmonary valve competence whenever possible. A "valve sparing approach" is easily applied to individuals with adequate pulmonary annulus size [7-10]. However, in patients with borderline pulmonary valve annulus sizes, this approach necessitates balancing some degree of residual RVOT obstruction against the obligate insufficiency associated with a transannular patch, which renders the pulmonary valve incompetent. Consensus is lacking on the size of the pulmonary annulus and the acceptable degree of residual outflow tract obstruction that is amenable to a valve sparing approach [7,8,11]. Though there is increasing emphasis on preservation of pulmonary valve function, two large database studies (the Society of Thoracic Surgeons 2002 to 2007 and the European Association for Cardiothoracic Surgery Congenital Database 1999 to 2011) demonstrated that ventriculotomy with transannular patch repair was the most common strategy for repair of TOF during that era [4,12].

An alternate surgical procedure is insertion of a valved conduit from the RV to the distal main pulmonary artery (PA) (figure 2). However, these conduits have no growth potential and they can become stenotic over time [13]. In addition, the conduit's prosthetic valve can develop stenosis and/or regurgitation. A monocusp valve may also be placed in the RVOT at the time of transannular patch in an attempt to decrease pulmonary insufficiency. However, it is unclear whether the presence of these valves affects the postoperative course or severity of pulmonary insufficiency. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Chronic pulmonary regurgitation'.)

Historically, TOF repair was performed in two staged procedures: a palliative shunt in early infancy followed by intracardiac repair later in childhood. However, this approach has been replaced with primary intracardiac repair [4,5,14-17]. Palliative shunts are reserved for cases wherein primary repair is not feasible. (See 'Palliative intervention' below.)

Timing — Surgery is usually performed electively in the first year of life; most repairs are performed before age six months [4]. The timing and choice of surgical intervention is based on individual patient characteristics and center-specific practice.

●Infants without severe RVOT obstruction – If the RVOT obstruction is not severe and the patient can be managed medically, it is generally preferable to defer elective surgical repair until after the neonatal period. This allows pulmonary vascular resistance to decline and gives time for the infant to grow to a larger size. Elective surgery is typically performed around three to four months of age.

●Neonates with severe RVOT obstruction – Neonates with more severe RVOT obstruction and/or ductal dependency may require early surgical or transcatheter intervention within the neonatal period. Options for these neonates include early primary repair or staged repair (ie, initial palliative procedure in the neonatal period followed by later elective complete repair). Surgical practice varies between centers, and the optimal approach is uncertain. For some patients, primary surgical repair may not be feasible due to the size of the infant (eg, preterm infants) or anatomy (eg, unfavorable coronary anatomy). Palliative shunts, RVOT stents, or ductal stents may be required in such cases. (See 'Palliative intervention' below.)

For patients with TOF who require intervention in the neonatal period, the advantage of primary repair is that it reduces the total number of surgeries required [16,17]. The main disadvantage is that risk of surgery may be increased in this setting [18-20]. In a meta-analysis of eight observational studies, mortality was higher for neonates who underwent early compete repair compared with later repair (6 versus 1 percent, respectively) [19]. However, most of these studies were not able to adequately control for severity of RVOT obstruction and other factors that impact surgical decision-making. Thus, the higher mortality rate observed in neonates undergoing repair may be a reflection of their higher baseline risk rather than the impact of the timing of surgery.

Studies addressing the question of whether outcomes differ between the two surgical approaches in neonates (early primary repair versus staged repair) have reached somewhat different conclusions [16,17,20,21]. One retrospective multicenter study of 2363 neonates with TOF who underwent early intervention found that primary repair was associated with higher mortality during the initial hospitalization compared with staged repair (odds ratio 1.72, 95% CI 1.15-2.62) and higher two-year mortality (hazard ratio 1.51, 95% CI 1.05-2.06) [20]. However, the study was limited by the lack of robust clinical details in the dataset used (an administrative database of hospital discharge and billing information). Thus, the investigators were not able to adequately control for many clinically important factors. In addition, a large proportion of the cohort (42 percent) had limited follow-up data available.

Similarly, in a multicenter study of 572 infants with cyanotic TOF who underwent staged repair (n = 342) or primary complete repair (n = 230), after adjusting for patient-related factors, early mortality and neonatal morbidity were higher in primary repair group, but cumulative morbidity and reinterventions where higher in the staged repair group [21]. These findings suggest potential benefits to each strategy.

Smaller single-center retrospective studies have reported equivalent outcomes for early complete repair and staged repair, with comparable mortality and fewer total surgical procedures and hospitalizations with early complete repair [16,17].

Additional prospective data are needed to more definitively answer the question of which approach is best. In the meantime, either approach is acceptable.

Perioperative complications — Complications in the immediate postoperative period after TOF repair include [5,14,15,18,22,23]:

●Residual lesions – Residual lesions such as VSDs and RVOT obstruction may persist. In some cases, reoperations or interventional catheterization may be needed if these lesions are hemodynamically significant. Residual VSDs may be "intramural defects" and more challenging to identify intraoperatively or by imaging. Intervention for residual RVOT obstruction is generally warranted for RV pressures ≥70 percent systemic pressure. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Residual RVOT obstruction'.)

Small atrial communications are often purposefully retained at the time of operative repair to allow atrial decompression (ie, as a "pop-off" communication allowing right-to-left shunting) to maintain cardiac output and prevent postoperative RV failure, albeit at the expense of a lower arterial oxygen saturation. These atrial communications generally do not require intervention.

●Other – Other perioperative complications may include low cardiac output, cardiopulmonary arrest, arrhythmia, heart block, bleeding, and PA branch stenosis.

In a report of 277 infants who underwent elective primary repair at a single center, 12 percent had at least one postoperative complication, including reoperation for bleeding (4 percent), cardiopulmonary arrest (2 percent), residual lesions (1 percent), pacemaker placement (0.4 percent), and PA branch stenosis requiring stent placement (0.4 percent) [22]. Similar findings were noted in a study using a large multicenter administrative dataset of 2859 infants <6 months old who underwent TOF repair from 2004 through 2010 [18]. Reported complications included dysrhythmias (9 percent), need for catheter-based intervention (3 percent), pacemaker placement (1.4 percent), extracorporeal membrane oxygenation support (1.3 percent), and surgical revision (1 percent).

Chronic postoperative complications that may require subsequent reintervention include pulmonary regurgitation, PA branch stenosis, and residual RVOT obstruction. These issues are discussed separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term complications'.)

Children with pulmonary atresia are more likely to require reoperation than those with pulmonary stenosis [5]. This is discussed separately. (See "Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCAs)", section on 'Prognosis'.)

Perioperative mortality — Reported perioperative mortality rates for neonates and young infants undergoing surgical repair of TOF range from 0 to 3 percent [5,14,15,18,22,23].

In a single-center report of the surgical outcomes of 277 low-risk infants (ie, none had required previous intervention of intensive care, none had hypercyanotic episodes, all had been discharged home after birth, all were ≤6 months old at the time of surgery, and the repair was elective in all cases), there were no perioperative deaths [22].

As previously discussed, the degree of RVOT obstruction and need for early surgery within the neonatal period appear to be risk factors for perioperative complications and early mortality. (See 'Timing' above.)

In a retrospective study of 4698 patients who underwent complete repair of TOF from 2004 through 2010, hospital mortality for the entire cohort was 1.3 percent [18]. Mortality rates varied depending on the patient's age at surgery as follows: 6.4 percent for those <1 month old, 1.9 percent for those 1 to <3 months old, 1.1 percent for those 3 to <6 months old, and 1.1 percent for those ≥6 months. (See 'Timing' above.)

Palliative intervention — A small subset of patients with TOF require early surgical or transcatheter palliative intervention before complete repair is performed.

Palliative intervention allows deferral of elective complete repair by providing stable pulmonary blood flow required for survival. Palliative intervention has traditionally consisted of surgical placement of a systemic-to-pulmonary connection. However, experience with transcatheter intervention (eg, stenting of the ductus arteriosus or RVOT) is growing, and these procedures have become an attractive alternative method to provide a source of pulmonary blood flow.

Indications — Patients selected for early palliative intervention may include:

●Infants who have severe RVOT obstruction

●Infants who are too small to undergo complete repair (eg, preterm infants)

●Infants with a medically refractory severe hypercyanotic ("tet") spell

●Infants with coronary anatomy complicating initial complete repair in the neonatal period

●Infants with PA hypoplasia who would not tolerate biventricular repair

Surgical shunts — Palliative shunts include the modified Blalock-Thomas-Taussig shunt (mBTTS) and central shunts. In the mBTTS, a synthetic graft is placed from the innominate or subclavian artery to the ipsilateral PA (figure 3).

Ductal or RVOT stenting — Transcatheter implantation of a ductal stent is used at many centers as an alternative to the mBTTS for infants with TOF and those with other forms of cyanotic congenital heart disease (CHD) [24,25]. In a meta-analysis of six retrospective studies comparing ductal stenting versus surgical shunt placement in 757 patients with various cyanotic CHD defects (TOF accounted for 6 percent), ductal stenting was associated with lower risk of postprocedural complications, lower need for mechanical circulatory support, and shorter hospital length of stay [26]. Rates of unplanned reintervention were similar in both groups (26 versus 23 percent; hazard ratio [HR] 1.39, 95% CI 0.70-2.78). Mortality was lower in the ductal stenting group, but the difference was not statistically significant (8.2 versus 11.8 percent; HR, 0.71 95% CI 0.26-1.93).

Stenting of the RVOT has also been described as an alternative to surgical shunt placement [27-29].

As experience with these procedures increases, they are becoming more attractive alternatives for neonatal palliation [24,25,27,29-31]. Use of this approach in other forms of cyanotic CHD (eg, hypoplastic left heart syndrome) is discussed separately. (See "Hypoplastic left heart syndrome: Management and outcome", section on 'Stage I hybrid procedure'.)

Surgical repair in adults — Although it is now a rare occurrence, TOF remains the most common unrepaired cyanotic CHD defect in adults. Complete repair is feasible in adults and may improve function. However, there is an increased operative risk compared with younger patients, and repair is often complicated by previous palliative surgery and the need for pulmonary valve replacement (PVR) or preservation. This issue is discussed separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Repair in adulthood'.)

LONG-TERM HEALTH CARE MAINTENANCE — Longitudinal follow-up care is required in all patients with TOF, in conjunction with a cardiologist with expertise in congenital heart disease (CHD). Clinicians need to know the associated complications following surgical repair, which can include chronic pulmonary regurgitation, right ventricular (RV) dysfunction, residual RV outflow tract (RVOT) obstruction, aortic root dilation, endocarditis, arrhythmias, and sudden cardiac death (table 1). Care is focused on identifying, managing, and preventing these long-term sequelae. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term complications'.)

Routine health care visits — At routine health care visits, the history and physical examination should include assessment of the patient's cardiac status, including:

●Episodes of palpitations, dizziness, or syncope, which may suggest an underlying arrhythmia

●Dyspnea or decreased exercise tolerance, which may suggest ventricular dysfunction

●Irregular pulse indicative of an underlying arrhythmia

●New murmurs on auscultation, which may suggest pulmonary or tricuspid regurgitation, pulmonary or branch pulmonary artery (PA) stenosis, or aortic insufficiency

●Signs of heart failure include pulmonary congestion, jugular venous distension, peripheral edema, and hepatomegaly

Cardiology follow-up — Patients who have undergone TOF repair require lifelong follow-up with a cardiologist with expertise in CHD. Follow-up visits occur frequently in the first year after surgery and are then spaced out if the child is doing well. Follow-up should occur at least annually throughout childhood, with more frequent visits if acute concerns arise. Our suggested schedule for follow-up cardiac testing is summarized in the table (table 2) and discussed in detail separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term follow-up'.)

Endocarditis prophylaxis — To reduce the risk of endocarditis, patients with repaired TOF should maintain good oral hygiene and receive timely treatment of infections. Antibiotic prophylaxis may be required before certain dental, oral, or invasive airway procedures (eg, routine dental cleaning, tooth extraction, adenotonsillectomy, cleft lip or palate repair) to reduce the risk of infective endocarditis. Prophylaxis is not necessary prior to gastrointestinal procedures (eg, endoscopy, colonoscopy) or genitourinary procedures (eg, cystoscopy, voiding cystourethrogram) unless the patient has an active infection.

Antibiotic prophylaxis prior to relevant procedures is recommended during the first six months after the corrective surgery. Prophylaxis is also recommended in patients who have prosthetic heart valves, in whom prosthetic material was used for cardiac valve surgery, or if there are residual defects at or adjacent to the site of a prosthetic device or material.

The approach to determining the need for prophylaxis is summarized in the figure (algorithm 1) and discussed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Immunizations — Children with TOF should receive all routine childhood vaccinations, including pneumococcal vaccine, yearly influenza vaccine, COVID-19 vaccine, and respiratory syncytial virus (RSV) immunoprophylaxis for eligible infants. (See "Standard immunizations for children and adolescents: Overview" and "Pneumococcal vaccination in children" and "Seasonal influenza in children: Prevention with vaccines" and "COVID-19: Vaccines", section on 'Children' and "Respiratory syncytial virus infection: Prevention in infants and children".)

Sports participation — Before participation in competitive sports, patients with TOF (repaired or unrepaired) should undergo evaluation, including clinical assessment, ECG, imaging assessment of ventricular function (typically with echocardiogram), and exercise testing [32]. Additional details are provided separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Sports participation'.)

LONG-TERM OUTCOMES — For patients who undergo surgical correction of TOF, the long-term prognosis is generally good; however, there is a risk of chronic cardiac complications.

Long-term complications — Patients with repaired TOF require long-term follow-up as they are at risk for chronic postoperative complications, as summarized in the table (table 1) and discussed in detail separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term complications'.)

Survival

●Without repair – Unrepaired TOF is associated with poor survival, with one-half of affected individuals dying in the first few years of life and most uncorrected patients not living beyond the third decade [33].

●Survival after repair – Long-term survival is excellent following TOF repair. In a study from a single center of 734 patients who underwent TOF repair in early childhood (median age 17 months) between 1986 and 2007 with a median follow-up of 12.5 years, overall survival rates were 95, 93, and 93 percent at 10, 20, and 25 years, respectively [34]. Other large series have reported similar survival rates following TOF repair in the modern era [35-38]. Arrhythmia and heart failure leading to sudden cardiac death are the most common causes of late death following surgical repair.

Survival has improved considerably with advances in surgical techniques. In a report from a single institution of 570 patients who underwent TOF repair (either as a primary repair or following initial palliative surgery) between 1953 and 2008, the rate of early mortality (ie, death within 30 days of surgery) declined steadily throughout the study period from 40 percent in the earliest era (1953 to 1971) to 0.6 percent in the later era (2000 to 2008) [35]. Late mortality (ie, death beyond 30 days) for the entire cohort was 7.9 percent over a median follow-up of 15.8 years.

Neurodevelopmental outcomes — Long-term follow-up of children with TOF demonstrates some impairments in cognitive and motor development. In two studies, children with TOF (5 to 12 years after surgical correction), when compared with healthy children, had lower scores on cognitive testing, mild impairment of fine motor skills, and difficulties with language tasks [39,40]. In another study, adolescents with TOF scored lower on psychosocial testing compared with healthy referents [41]. Lower scores were also associated with concurrent executive dysfunction and attention deficit hyperactivity disorder.

All children with TOF should undergo appropriate developmental-behavioral surveillance and screening [42]. If concerns are identified, early referral to a developmental specialist is critical. (See "Developmental-behavioral surveillance and screening in primary care".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Congenital heart disease in infants and children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Tetralogy of Fallot (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Initial medical management – Infants with tetralogy of Fallot (TOF) (figure 1) may require initial medical therapy depending on the degree of right ventricular outflow tract (RVOT) obstruction (see 'Initial medical management' above):

•Severe RVOT obstruction – Neonates with severe RVOT obstruction may require intravenous (IV) prostaglandin therapy (alprostadil), ductal stenting, RVOT stenting, or palliative shunt placement to maintain adequate pulmonary blood flow pending surgical repair. (See 'Neonates with severe RVOT obstruction' above and 'Palliative intervention' above and "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1'.)

•Hypercyanotic spells – Patients who experience hypercyanotic ("tet") spells require prompt intervention. Management is stepwise and begins with knee-chest positioning and supplemental oxygen. If these measures fail, we recommend IV morphine and IV fluid bolus (Grade 1C). If symptoms persist, the next steps are IV beta blockers followed by IV phenylephrine, if necessary. A palliative surgical procedure may be needed if medical therapy fails. (See 'Tet spells' above.)

•Heart failure symptoms – Patients with minimal RVOT obstruction and increased pulmonary blood flow may develop heart failure symptoms requiring pharmacologic therapy (diuretic therapy and digoxin). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are generally not used in this setting. (See 'Heart failure' above and "Heart failure in children: Management".)

●Surgical repair – For most infants with TOF, we suggest primary complete repair rather than a staged approach (ie, initial palliative intervention followed by intracardiac repair) (Grade 2C). Surgical repair is typically performed between three to six months of age and consists of patch closure of the ventricular septal defect (VSD) and enlargement of the RVOT with relief of all sources of obstruction (figure 2). (See 'Surgical repair' above.)

●Long-term complications after repair – Patients who have undergone TOF repair are at risk for long-term postoperative complications, which may require reintervention. These are summarized in the table (table 1) and discussed in greater detail separately (see "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term complications'):

●Long-term health care maintenance – Longitudinal follow-up care is required in all patients with TOF, in conjunction with a cardiologist with expertise in congenital heart disease. Important aspects of long-term health care maintenance in children with TOF include administering routine childhood vaccinations, monitoring growth parameters, monitoring for long-term complications (table 1), and providing guidance regarding exercise and sports participation. (See 'Long-term health care maintenance' above and 'Sports participation' above.)

Additional details regarding long-term cardiology follow-up summarized in the table (table 2) and discussed separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term follow-up'.)

Patients with TOF may require antibiotic prophylaxis before certain dental procedures. The approach to determining the need for prophylaxis is summarized in the figure (algorithm 1) and discussed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

●Outcome – Surgical correction has resulted in excellent long-term survival, particularly for patients who are operated on at a young age, for whom survival is >90 percent 25 years after repair. Heart failure and arrhythmia leading to SCD are the most common causes of late death following surgical repair. Long-term cardiovascular sequelae are common among adult survivors of TOF repair, and approximately one-third of patients require reoperation, most commonly for pulmonary valve replacement. In addition, patients with TOF are at risk for long-term neurodevelopmental impairment. (See 'Long-term outcomes' above and "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Long-term complications'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas Graham Jr, MD, who contributed to an earlier version of this topic review.