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. The pathophysiology, clinical features, and diagnosis of this defect are reviewed elsewhere. (See "Pathophysiology, clinical features, and diagnosis of tetralogy of Fallot".)
TOF with pulmonary atresia is discussed separately. (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 almost total 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 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 — Some patients with minimal obstruction and increased pulmonary blood flow may develop heart failure symptoms and require pharmacologic treatment that includes digoxin and a loop diuretic (eg, furosemide). 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 "Pathophysiology, clinical features, and diagnosis of tetralogy of Fallot", section on 'Tet spells' and "Heart failure in children: Management".)
Antibiotic prophylaxis — Based on the American Heart Association guidelines for all patients with unrepaired cyanotic congenital heart disease, antibiotic prophylaxis is administered to prevent bacterial endocarditis until surgical correction is performed. (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:
●Relief of RVOT obstruction
●Complete separation between the pulmonary and systemic circulations
●Preservation of RV function
●Minimize postprocedure pulmonary valvular incompetence
The surgery consists of patch closure of the ventricular septal defect (VSD) and enlargement of the RVOT, 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 [7-9]. 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 [7,8,10]. 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 remains the most common strategy for repair of TOF [4,11].
An alternate surgical procedure is insertion of a valved conduit from the RV to the distal main PA (figure 2). However, stenosis and/or regurgitation of the conduit prosthetic valve, as well as stenosis of the conduit, can occur [12]. 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 'Chronic pulmonary regurgitation' below.)
Historically, TOF repair was performed in two staged procedures: a palliative shunt in early infancy followed by intracardiac repair later in childhood. However, at most centers this approach has been replaced with primary intracardiac repair [4,5,13-16]. 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, with the majority of repairs 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 [15,16]. The main disadvantage is that risk of surgery may be increased in this setting [17-19]. 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) [18]. 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 [15,16,19]. One retrospective multicenter study of 2363 neonates with TOF who underwent early intervention (1032 infants underwent early primary complete repair; 1331 underwent staged repair) found that primary repair was associated with higher mortality during the initial hospitalization (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) [19]. However, the study was limited by the lack of robust clinical details in the dataset used (which is 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) did not have follow-up data available at two years.
By contrast, 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 [15,16].
Additional prospective data are needed to more definitively answer the question of which approach is best. In the meantime, either approach is reasonable.
Perioperative complications — Complications in the immediate postoperative period after TOF repair include [5,13,14,17,20,21]:
●Residual lesions – Residual lesions such as VSDs and RVOT obstruction may persist. In some cases, reoperations or interventional catheterization may 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.
Small atrial communications are often purposefully retained at the time of operative repair to allow atrial decompression (ie, as a "popoff" 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) [20]. 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 [17]. 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 below. (See 'Chronic postoperative complications' below.)
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 [5,13,14,17,20,21].
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 [20].
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. 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 [17]. 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. 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
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, as experience increases with transcatheter intervention (eg, stenting of the ductus arteriosus or RVOT), these procedures are becoming an attractive alternative method to provide a source of pulmonary blood flow.
●Palliative shunts – Palliative shunts include the modified Blalock-Thomas-Taussig shunt (also commonly called the modified Blalock-Taussig shunt [mBTS]) and central shunts. In the mBTS, 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 some centers as an alternative to the mBTS for infants with TOF and those with other forms of cyanotic congenital heart disease (CHD) [22,23]. Stenting of the RVOT has also been described as an alternative to surgical shunt placement [24-26]. As experience with these procedures increases, they are becoming more attractive alternatives for neonatal palliation [22-24,26-28]. 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'.)
Adults — Although it is now a rare occurrence, TOF remains the most common cyanotic CHD defect to reach adulthood without surgical repair. Even in older adult patients, complete repair is feasible, resulting in improved 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.
In a case series of 52 adult patients (≥40 years old) who underwent TOF repair between 1970 and 2007, procedures for repair included PVR (n = 10), transannular patch (n = 10), and native pulmonary valve preservation (n = 32) [29]. Approximately one-half the patients in the series had had previous palliative surgery. Three patients died during the perioperative period, and during a mean follow-up of 15 years, 29 of the 49 remaining survivors died. The 10-year survival rate was lower compared with an age- and sex-matched population (73 versus 91 percent) and compared with patients with TOF operated on at a younger age who had an expected 20-year survival rate of 86 percent. Of the 49 survivors, 42 had improvement in their New York Heart Association functional class and only 5 patients remained in functional class III or IV (table 1).
In two other case series of TOF repair in adulthood, intraoperative mortality was 2.5 percent and in-hospital mortality was 16 percent [30,31].
CHRONIC POSTOPERATIVE COMPLICATIONS — Patients after intracardiac repair for TOF require long-term follow-up as they are at risk for the chronic postoperative complications, including pulmonary regurgitation with associated right ventricular (RV) enlargement, residual RV outflow tract (RVOT) obstruction, RV dysfunction, aortic root dilation and aortic valve insufficiency, arrhythmias including atrial tachycardia (AT) and ventricular tachycardia (VT), and sudden cardiac death (SCD) [32-34].
Chronic pulmonary regurgitation — Intracardiac repair with a transannular RVOT patch results in obligate chronic severe pulmonary regurgitation. Insufficiency may also occur in patients who have monocusp valves placed at the time of initial repair or who have a valved conduit from the RV to the pulmonary artery (PA) as these valves become progressively incompetent over time. The degree of insufficiency may vary depending on surgical approach and on the presence or absence of associated PA stenosis. In the setting of long-standing severe pulmonary regurgitation, the RV enlarges due to increased workload [35,36]. This may be associated with increasing tricuspid insufficiency, further contributing to RV enlargement.
Right ventricular enlargement and function — Patients with RV enlargement and with normal RV function are asymptomatic. However, they are at risk for the evolution of RV dysfunction, associated with decreased exercise tolerance, right heart failure, and arrhythmias (ie, VT, atrial flutter, and atrial fibrillation). The decline in RV function can also lead to left ventricular (LV) dysfunction due to septal shift and ventricular/ventricular interaction [35,37,38].
Pulmonary valve replacement and right ventricular function — Pulmonary valve replacement (PVR) may be necessary to restore pulmonary valve competence and improve RV function [39-43]. Although optimal timing of PVR remains uncertain, this option should be considered in patients with any of the following:
●Symptoms attributable to pulmonary regurgitation/RV dysfunction
●Moderate or severe RV volume overload
●RV dysfunction
●Tricuspid valve regurgitation
●Arrhythmias attributable to the right heart enlargement/dysfunction from pulmonary valve regurgitation
Ideally, PVR is performed before severe RV dysfunction develops.
Among 452 patients enrolled in a multicenter (INDICATOR) cohort followed for a median of 6.5 years after PVR, pre-PVR findings of RV ejection fraction <40 percent, RV mass-to-volume >0.45 g/mL, age at PVR >28 years, and RV systolic pressure >40 mmHg by Doppler were associated with shorter time to death, aborted SCD, or sustained VT and these risk factors were additive [44].
Based on data from studies using magnetic resonance imaging (MRI), the threshold degree of dilation appears to be end diastolic volumes exceeding 160 to 170 mL/m2 or end systolic volumes exceeding 80 to 85 mL/m2 beyond which restoration of normal RV volume cannot be achieved with subsequent valve replacement [45-47]. It is important to note that while RV volumes decreased significantly with valve replacement, ejection fractions were not significantly changed by valve replacement. These data, paired with exercise data in this population, underscore the need to proceed with PVR before severe RV dysfunction develops. Although aerobic exercise capacity improves substantially after PVR, studies have shown that patients will fail to demonstrate improvement in RV function and exercise capacity when intervention occurs too late in the disease process [48,49]. A small single-center cohort demonstrated similar overall survival at median follow-up of 69 months among 46 patients with mild RV dilation (mean RV end-diastolic volume index 127 mL/m2) and 42 patients with severe dilation (mean RV end-diastolic volume index 191 mL/m2), but cardiac adverse events were more frequent at 5- and 10-year follow-up among the severely dilated patients [50].
PVR may be performed surgically or percutaneously:
●Surgical PVR – The overall survival following surgical PVR is excellent, with reported survival of 97, 96, and 92 percent at one, three, and five years follow-up, respectively, post-valve replacement in adults, which continues to improve over time [51]. There is also a low rate of reintervention of 2 and 4 percent at follow-up at 5 and 10 years, respectively.
●Transcatheter PVR (TPVR) – TPVR is an alternative option to surgical PVR [52-56]. The three devices approved by the US Food and Drug Administration for this indication include:
•Melody valve (Medtronic) – A valve fashioned from a bovine jugular vein valve mounted on a balloon-expandable intravascular stent. This valve is approved for conduits ≥16 mm at the time of implantation with a recommended maximum diameter of 22 mm [57].
•SAPIEN XT valve (Edwards) – A valve fashioned from bovine pericardium and mounted on a balloon expandable intravascular stent. This valve comes in diameters of 23 mm, 26 mm, and 29 mm [58].
•Harmony Valve (Medtronic) – A self-expanding porcine pericardial valve mounted within a pericardial tube that is supported by a nitinol framework. The valve is specifically designed for use in large-diameter native outflow tracts. The valve comes in two sizes (22 and 25) with different inflow and outflow sizes designed to accommodate a variety of native outflow tract morphologies [59].
Reintervention may be required for stent fracture, device failure with recurrent stenosis, residual stenosis not relieved by the stent, or infection [55,60].
In one report, the five-year freedom from reintervention and freedom from explantation rates following TPVR were 76 percent and 92 percent, respectively [55]. The most common reason for reintervention was recurrent stenosis related to stent fracture.
Relieving conduit obstruction with bare metal stent implantation prior to implantation of the percutaneous pulmonary valve may diminish the risk of pulmonary valve prosthesis-related stent fracture [61,62]. In an analysis of data from three prospective multicenter studies evaluating TPVR in patients with TOF, the five-year freedom from reintervention rate among patients who had valves placed into previously stentless conduits (n = 251) was 73 percent [62]. Placement of a new pre-stent prior to valve implantation was associated with decreased risk of pulmonary valve prosthesis-related stent fracture (hazard ratio 0.23, 95% CI 0.10-0.55) and reintervention (hazard ratio 0.53, 95% CI 0.30-0.93).
Acute life-threatening complications of TPVR are uncommon. In a case series of 152 patients undergoing TPVR, 6 patients (4 percent) had acute complications requiring rescue surgery including homograft rupture, dislodgement of the stented valve, occlusion of the right PA, and compression of the left coronary artery [63].
There appears to be an increased risk of endocarditis in patients with bovine jugular vein prostheses. The mechanism is incompletely understood [64,65]. In a 2017 meta-analysis of 50 studies (most were observational) of >7000 patients who underwent RV-to-PA conduit or percutaneous pulmonary valve implantation, the overall incidence of endocarditis was 2.6 percent; the incidence was higher in bovine jugular vein valves compared with other valves (5.4 versus 1.2 percent) [66].
●Mechanical PVR – Mechanical PVR is rarely performed but may be considered in patients with mechanical valve prostheses in another valve position, need for chronic warfarin anticoagulation, or multiple prior operative interventions. These prosthetic valves have been shown to be safe to use [67].
Degeneration of the tissue valves can be expected over time, and data regarding this issue are accruing. MRI data evaluating patients with repaired TOF who have undergone surgical or TPVR demonstrated that the favorable RV remodeling noted initially after replacement deteriorated over 7 to 10 years in many of the patients, due to deterioration of the prosthesis [68]. Measures of RV size and function at 7 to 10 years after PVR were similar to pre-replacement values, highlighting again the need for referral for valve replacement before the evolution of marked RV dilation and before deterioration of RV performance. Though it was encouraging that 69 percent of patients were shown to have low RV pressure and volume loads 7 to 10 years after PVR, these data emphasize the need for continued surveillance of RV size and function post-PVR [69].
Residual RVOT — Residual RVOT obstruction can persist after the original intracardiac operation due to hypertrophied subvalvar muscle, annular hypoplasia, pulmonary valve stenosis, supravalvar pulmonary stenosis, or branch PA stenosis [13]. In particular, left PA stenosis in the region of the ductal insertion is a common cause of RVOT obstruction. Mild obstruction is usually well tolerated, but severe obstruction may require reoperation or catheter-based intervention. Relief of PA stenosis by balloon dilation or stenting may be necessary prior to PVR [70].
Aortic root and valve dilation — A substantial portion of adult TOF patients have ascending aorta dilation and are at risk for the development of aortic valve insufficiency over time [71-73]; there have been case reports of patients with aortic dissection, though these complications appear rare.
In two large case series, approximately 30 to 50 percent of adult patients with repaired TOF had ascending aorta dilation [72,73]. Moderate to severe aortic valve regurgitation was observed in 3.5 percent of patients [73]. Aortic valve repair or replacement was performed in 1 to 2 percent or patients and another 1 to 2 percent required aortic root replacement. No patients had aortic dissection and there were no deaths due to aortic disease.
Arrhythmias
Incidence and risk factors — Following surgical repair for TOF, patients are at risk of development of atrial and ventricular arrhythmias. (See "Atrial arrhythmias (including AV block) in congenital heart disease".)
In a multicenter, cross-sectional study of 566 adult patients with repaired TOF (mean age 36.8 years), 43 percent had a sustained arrhythmia or arrhythmia intervention [74]. The frequency of arrhythmias markedly increased after 45 years of age. In this cohort, the prevalence of AT was 20 percent and ventricular arrhythmia was 15 percent.
In a second multicenter series of 793 patients (mean age at repair 8.2 years) followed for a mean of 21 years, 33 patients developed sustained monomorphic VT, 29 had new-onset sustained atrial flutter or fibrillation, and 16 died suddenly [75].
Reported risk factors according to the type of arrhythmias include:
●VT – Increasing number of cardiac operations [74], LV diastolic dysfunction [74], pulmonary regurgitation [75,76], electrocardiographic (ECG) finding of prolonged QRS duration [74,75], and older age at repair [30,31].
●AT – For all ATs, increasing number of cardiac operations [74] and older age at repair [75]. Risk factors for specific AT are as follows:
•Atrial fibrillation/flutter – Left atrial dilation, lower LV ejection fraction, and tricuspid regurgitation [74,75]
•Intraatrial reentrant tachycardia – Right atrial enlargement and hypertension [74]
Of note, because the ECG typically demonstrates a right bundle branch block pattern following TOF repair, most ATs in these patients are wide complex (with right bundle branch block) regardless of their specific mechanism. VT may display a typical left bundle branch block pattern since it generally originates from the RV. However, VT can originate from one of several potential anatomic isthmuses within the RV and, depending on the direction of conduction through the critical isthmus, a right bundle branch block pattern can sometimes be seen despite origin in the RV [77]. Monomorphic VT is dependent upon a region of slow conduction that may be amenable to radiofrequency catheter ablation or intraoperative cryoablation. However, the isthmus may not be reliably associated with the ventriculotomy scar itself, so preoperative mapping is warranted to define the precise VT substrate [78]. (See 'Role of electrophysiology study' below.)
Although pulmonary valve regurgitation and RV dilation are associated with VT, the risk of VT is not eliminated with PVR [79]. In patients known to have VT preoperatively or considered to be at high risk based upon a positive electrophysiology study (EPS), testing should be repeated postoperatively. If there is persistence of inducible VT, radiofrequency ablation and/or placement of an implantable cardioverter-defibrillator (ICD) should be considered [80]. (See 'Role of electrophysiology study' below and 'Sudden cardiac death' below.)
In a cohort of 200 adult patients undergoing PVR, sustained VT or sudden death was uncommon in the first year of follow-up but occurred in 19 patients over a median follow-up of 6.7 years [79]. Surgical cryoablation in 22 high-risk patients may have resulted in risk reduction, with VT occurring in only one patient. Prior VT and LV dysfunction were correlated with increased risk of VT or sudden death.
In another cohort of 165 patients with TOF and ICDs (placed for secondary prevention in approximately two-thirds of the cohort), the burden of appropriate ICD shocks before and after PVR was reduced from 44 to 13 per 100 patient-years [81].
In another study of 47 patients with TOF undergoing ICD for secondary prevention of VT, 43 percent of patients had VT ablation performed prior to ICD implantation, including transcatheter ablation in 12 patients and surgical ablation at the time of surgical PVR in eight patients [82]. Over median follow-up of 6.7 years, patients who had undergone prior ablation were less likely to receive appropriate ICD shocks compared with those who had not (10 versus 37 percent, respectively).
Role of electrophysiology study — EPS with ventricular stimulation aids in the assessment for VT risk in patients with TOF and, in selected cases, may be combined with radiofrequency ablation. While it is not routine for all patients with TOF, EPS with ventricular stimulation is appropriate for the following patients:
●Patients with symptomatic VT.
●Patients with additional risk factors for VT (eg, unexplained syncope, sustained palpitations, or sustained VT) [83].
●Patients who have nonsustained VT on monitoring.
●Older patients with widening of the QRS complex on ECG if they are about to undergo or have undergone PVR.
●Patients with TOF undergoing EPS and catheter ablation for atrial arrhythmias. In these patients, programmed ventricular stimulation to assess for susceptibility to VT is reasonable since risk factors are similar for both arrhythmias in this population.
●Patients with repaired TOF and recurrent VT resulting in repeated ICD shocks.
In a multicenter study of 252 patients with repaired TOF who underwent EPS with ventricular stimulation, sustained monomorphic VT and polymorphic VT were observed in 30 and 4 percent of patients, respectively [84]. After adjusting for other factors, inducible VT remained a strong predictor for future clinical VT or SCD. Its predictive value was greater in patients with underlying risk factors for VT compared with those without risks (positive predictive value 68 versus 25 percent and negative predictive value 86 versus 99 percent, respectively).
Limited data suggest that cardiac MRI findings may correlate with electroanatomic mapping [85]. However, the ability of this methodology to reliably predict VT is uncertain. Thus, invasive EPS with electroanatomic mapping and assessment of the conduction isthmuses remain essential in evaluation of the VT substrate.
When a defined substrate can be targeted, catheter ablation is a reasonable treatment option [86,87]. In a study of 78 patients with TOF who underwent EPS with ventricular stimulation and electroanatomic mapping, slowly conducting anatomic isthmuses were found in 92 percent of patients with inducible VT compared with only 4 percent of those without inducible VT [88]. However, QRS duration was similar in patients with and without inducible VT. Catheter ablation is discussed in greater detail separately. (See "Overview of catheter ablation of cardiac arrhythmias".)
Sudden cardiac death — SCD is an important cause of mortality after intracardiac repair of TOF. Identifying patients at risk for SCD and providing an effective intervention (eg, ICD implantation) could reduce long-term mortality; however, a reliable risk stratification schema is lacking in this patient population. Catheter ablation and/or ICD implantation should be considered in patients in whom stable monomorphic VT can be induced and mapped on EPS [89-92]. (See 'Role of electrophysiology study' above.)
For other patients at high risk for arrhythmias, including those with documented or sustained VT, ICD placement is recommended, even if VT cannot be induced or is not amenable to mapping [86,89,92-95]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)
In three large series of patients followed for up to 36 years, SCD occurred in 2 to 9 percent [75,96,97]. The majority of SCD is presumed to be due to ventricular arrhythmia [98-100].
In addition to inducible VT on EPS, other reported risk factors for SCD and/or VT include [86,101-103]:
●Prolonged QRS
●Older age at the time of repair
●Previous palliative shunt
●Higher number of thoracotomies
●RV dilation
●Ventricular dysfunction
●History of atrial arrhythmias
Outcomes following ICD placement were described in a multicenter study of 121 adult patients with TOF in whom ICDs were implanted for primary (56 percent) or secondary (44 percent) prevention of SCD [92]. At a median follow-up of 3.7 years after implantation, approximately 30 percent of patients received at least one appropriate and effective ICD discharge; the rate was similar in patients who had the ICD placed for primary or secondary prevention (8 versus 10 percent per year, respectively). Inappropriate shocks occurred in 6 percent of patients per year. In addition, 36 patients experienced complications: 6 due to periprocedural complications (eg, pneumothorax or hemothorax), 7 with late generator-related complications (eg, chronic pain, late infection, or malfunction), and 25 due to lead-related complications (eg, lead dislodgement, failure, or fracture). Nine patients died during the follow-up period, four due to heart failure and five due to SCD. Three of the five SCD deaths were attributed to presumed electromechanical dissociation because there were no tachyarrhythmias detected on ICD interrogation. One patient died after voluntary ICD inactivation, and one died after a prolonged ventricular tachyarrhythmia storm with exhaustion of ICD therapy.
Similar findings were noted in a report from a French registry that included data on 165 patients (mean age 42 years) with TOF and ICDs, 63 percent of whom had the ICD placed for secondary prevention [104]. Over a median follow-up of 6.8 years, 43 percent of patients received at least one appropriate ICD discharge. The rate was slightly lower in patients who had the ICD placed for primary compared with secondary prevention (7 versus 12 percent per year, respectively). For patients who underwent ICD placement for primary prevention, the frequency of appropriate ICD discharges was highest among those with ≥3 risk factors for SCD. Interestingly, in multivariate analyses, the only independent predictor of receiving appropriate ICD discharge was the presence of QRS fragmentation on ECG. Other studies have reported a correlation between the presence and extent of QRS fragmentation and the degree of RV dilation and dysfunction [105].
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 and also for the rare unoperated patients. As noted above, the most common complications following surgery include chronic pulmonary regurgitation, right ventricular (RV) enlargement, residual RV outflow tract (RVOT) obstruction, aortic root and valve dilation, arrhythmias, and sudden cardiac death. Care is focused on identifying and managing these long-term sequelae.
Routine health care visits — Routine health care visits are conducted at least yearly, with a focused history, physical examination, and testing [86,106].
The history and physical examination concentrates on the cardiac status of the patients.
●Episodes of palpitations, dizziness, or syncope are suggestive of an underlying arrhythmia
●Dyspnea or decreased exercise tolerance is suggestive of ventricular dysfunction
●Irregular pulse may suggest an underlying arrhythmia
●Murmurs detected by cardiac auscultation may be suggestive of 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
Tests — The following tests are performed on a routine basis, but frequency may vary depending on the patient's age, type of repair, new symptoms, or ongoing cardiac issues (such as arrhythmias, RV dilation, or RVOT obstruction):
●Echocardiography is recommended annually until the age of 10 years and every two years through adulthood [107]. The focus of echocardiography monitoring is to:
•Detect the presence and size of any residual septal defects
•Determine the severity of pulmonary insufficiency
•Determine if there is persistent RVOT obstruction, and if present, ascertain the severity and the site of obstruction
•Assess RV and left ventricular size, function, and wall motion
•Detect any aortic root dilation and/or aortic valve insufficiency
●ECG is performed yearly to assess cardiac rhythm and to evaluate QRS duration, which, if prolonged, is a risk factor for ventricular tachycardia (VT). (See 'Arrhythmias' above.)
●Holter monitor can be considered every three to four years or more frequently if symptoms or clinical concerns arise for arrhythmias.
●Cardiac MRI is an essential component to the postoperative assessment of patients with TOF and is the gold standard for assessment of chamber sizes and ventricular performance. It is generally performed in the adult patient every three years depending on the clinical concerns. The lack of radiation makes MRI ideal for serial evaluations. The measurement of RV size and performance is important in determining if pulmonary valve replacement should be considered. Assessment of all levels of the RVOT, including the branch PAs, is possible with this modality, allowing far more thorough evaluation than is possible with echocardiography. Quantitative assessment of flows to the left and right lungs may help guide surgical- and catheterization-based interventions. Evaluation of aortic size and regurgitant flow is also possible with this modality. Patients for whom MRI is not an option due to pacemaker or implantable cardioverter-defibrillator (ICD) placement should have evaluation of ventricular volumes and performance by computed tomography (CT) scan. (See "Clinical utility of cardiovascular magnetic resonance imaging".)
However, cardiac MRI is typically not performed in small children who require anesthesia (typically <10 years of age) unless indicated for specific clinical concerns that are best addressed with this modality. In older patients, when following RV size and function, MRI is recommended every three years in stable adult patients. MRI is performed more frequently (ie, every 12 months) for patients with the following clinical conditions [107]:
•Moderate RV dilation (RV end diastolic dimension >150 cc/m2)
•Progressive RV dilation (increase of >25 mL/m2 between studies)
•RV dysfunction (RV ejection fraction [EF] <38 percent or >6 percent decrease in EF between studies)
●Exercise testing provides an objective measurement of exercise capacity and may detect exertional arrhythmias. It is performed every three to four years in adolescents and adults.
●Cardiac catheterization is typically reserved for individuals when percutaneous intervention is being considered or if PA hypertension is suspected. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)
●Electrophysiologic study and mapping for patients who are at risk for VT. (See 'Sudden cardiac death' above and 'Role of electrophysiology study' above.)
Antibiotic prophylaxis — Antibiotic prophylaxis is recommended during the first six months after the corrective surgery. Prophylactic therapy is also recommended in patients who have prosthetic heart valves, in whom prosthetic material was used for cardiac valve surgery, or who still have residual defects at the site or adjacent to the site of a prosthetic device or material. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Pregnancy — Pregnancy is not recommended in patients with unrepaired TOF [86]. However, after corrective surgery, women with TOF generally have good maternal and infant outcomes if they do not have severe hemodynamic abnormalities before pregnancy [108-112]. A comprehensive cardiovascular evaluation by a congenital cardiac specialist is recommended prior to pregnancy to confirm there are no cardiovascular features that would be best treated before a pregnancy, or to suggest a pregnancy would be high risk and not advised.
A literature review of studies published between 1985 and 2007 evaluated the rates of complications during completed pregnancies among women with repaired TOF [113]:
●Maternal complications included arrhythmias in 13 of 204 pregnancies (6.4 percent) and heart failure in 5 of 211 pregnancies (2.4 percent). There were no cases of myocardial infarction, stroke, or cardiovascular mortality in 222 pregnancies.
●Fetal complications included premature delivery in 11 of 174 pregnancies (6.3 percent), fetal mortality in 1 of 222 pregnancies (0.5 percent), perinatal mortality in 3 of 222 pregnancies (1.4 percent), small for gestational age in 19 of 211 pregnancies (9 percent), and recurrent CHD of any type in 6 of 202 pregnancies (3 percent).
In addition, offspring are more likely to have congenital anomalies and genetic mutations, especially 22q11.2 microdeletion, compared with the general population [86]. Approximately 15 percent of patients with TOF and other conotruncal defects have chromosome 22q11.2 microdeletion [114]. Screening for 22q11.2 microdeletion should be considered in patients with conotruncal abnormalities prior to pregnancy in order to provide appropriate genetic counseling. In the absence of 22q11.2 deletion, the risk of a fetus having CHD is approximately 4 to 6 percent. In contrast, children born to a parent with 22q11.2 microdeletion have a 50 percent chance of having the deletion and its associated complications. (See "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis", section on 'Cardiac anomalies'.)
Because of the increased risk of congenital anomalies, fetal echocardiography should be offered to the mother in the second trimester [86].
The general care for a pregnant woman with CHD is discussed elsewhere. (See "Pregnancy in women with congenital heart disease: General principles".)
Sports participation — The 2015 scientific statement of the American Heart Association and American College of Cardiology provides competitive athletic participation guidelines for patients with CHD, including TOF [87]. Of note, because of the paucity of evidence regarding physical activity in patients with TOF, these guidelines were based largely on consensus opinions of conference participants. We concur with these recommendations but stress that, as with any guidelines, recommendations need to be tailored to the patient and a comprehensive evaluation by an experienced clinician is required.
●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.
●Patients with unrepaired TOF who are clinically stable and without clinical symptoms of heart failure may be considered for participation in only low-intensity class IA sports (figure 4).
●Patients with repaired TOF may be considered for participation in moderate- to high-intensity sports (figure 4) if they do not have evidence of clinically significant ventricular dysfunction (EF >50 percent), arrhythmias, or outflow tract obstruction. To meet these criteria, the patient must be able to complete an exercise test without evidence of exercise-induced arrhythmias, hypotension, ischemia, or other concerning clinical symptoms. (See "Physical activity and exercise in patients with congenital heart disease", section on 'Cardiopulmonary exercise testing'.)
●Patients with repaired TOF who have severe ventricular dysfunction (EF <40 percent), severe outflow tract obstruction, or recurrent or uncontrolled atrial or ventricular arrhythmias should be restricted from all competitive sports.
Physical activity and exercise in patients with CHD are discussed in greater detail separately. (See "Physical activity and exercise in patients with congenital heart disease".)
LONG-TERM OUTCOMES
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 [115].
Surgical survival and morbidity — For patients who undergo surgical correction of TOF, the long-term prognosis is generally good; however, as previously discussed, there is a risk of chronic cardiac complications. (See 'Chronic postoperative complications' above.)
●Survival – 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 [32,108,116,117]. 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) [32]. Late mortality (ie, death beyond 30 days) for the entire cohort was 7.9 percent over a median follow-up of 15.8 years.
●Cardiovascular morbidity – 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 (PVR) [34,116,117]. Patients undergoing transannular patch repair are at particularly high risk of needing reoperation [32]. (See 'Pulmonary valve replacement and right ventricular function' above.)
In a single institution report of 840 adult survivors who underwent corrective surgery for TOF in childhood (median age 6.9 years), right-sided cardiac findings included moderate to severe pulmonary regurgitation (54 percent) and mild right ventricular outflow tract obstruction (RVOT; one-third of the patients), and left-sided findings of mild aortic regurgitation (50 percent) and left ventricular hypertrophy and dilation [116]. Surgical reoperations were performed in 19 percent of adult survivors. Cardiorespiratory symptoms were reported in 45 percent of the cohort, which included palpitations (27 percent), dyspnea (21 percent), and chest pain (17 percent). Older patients were more likely to report poorer physical conditioning and were more likely to have echocardiographic abnormalities.
In another single institution study of 1085 patients who were operated on between 1964 and 2009, 36 percent of patients who survived to age 40 years had undergone PVR [117]. The mean age at time of PVR was 20 years. Patients who had survived beyond 35 years of age without requiring PVR and who had normal exercise capacity tended to have a mild degree of residual RVOT obstruction and small pulmonary annulus diameter (ie, Z-score <0.5).
The prevalence of cardiovascular morbidity among adults survivors was studied in the Euro Heart Survey of adult congenital heart disease, which followed 811 young adults (median age 26 years) with TOF for five years [108]. The majority of patients in this cohort had undergone previous repair, 40 percent with transannular patch. Complications noted over the study period included supraventricular arrhythmias (20 percent), ventricular arrhythmias (14 percent), endocarditis (4 percent), stroke or transient ischemic attack (4 percent), and myocardial infarction (1 percent). Data on the prevalence of pulmonary insufficiency and need for PVR were not available. Most patients had few or no symptoms, 93 percent were New York Heart Association class I or II (table 1), and 56 percent were on no medications. Diuretics, beta blockers, and angiotensin converting enzyme inhibitors were each taken in 11 to 15 percent, warfarin or other vitamin K antagonist in 9 percent, and antiarrhythmic drugs in 4 percent.
Neurodevelopmental outcome and quality of life — 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 intelligence tests, mild impairment of fine motor skills, and difficulties with language tasks [118,119]. In another study, adolescents with TOF scored lower on physical health and psychosocial testing than healthy referents [120]. 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 [121].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 5th to 6th 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 10th to 12th 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 – The need for medical intervention is dependent 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 obstruction and increased pulmonary blood flow may develop symptoms of heart failure and require pharmacologic treatment (loop 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 tetralogy of Fallot (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.)
●Chronic postoperative complications – Patients who have undergone TOF repair are at risk for chronic postoperative complications, which may require reintervention. These include (see 'Chronic postoperative complications' above and 'Surgical survival and morbidity' above):
•Pulmonary regurgitation with associated RV enlargement (see 'Chronic pulmonary regurgitation' above)
•Residual RVOT obstruction and RV dysfunction (see 'Residual RVOT' above)
•Aortic root dilation and aortic valve insufficiency (see 'Aortic root and valve dilation' above)
•Arrhythmias, including atrial and ventricular tachycardia (AT and VT) (see 'Arrhythmias' above)
●Long-term follow-up – Longitudinal follow-up care is required in all patients with TOF, in conjunction with a cardiologist with expertise in congenital heart disease. Follow-up care is focused on identifying and managing long-term complications. It encompasses annual or more frequent routine health care visits, with a focused cardiac history and physical examination. Routine cardiac testing depends upon the patient's age, type of repair, symptoms, and ongoing clinical concerns. Tests may include ECG, echocardiogram, Holter monitoring, exercise testing, and, occasionally, cardiac MRI or CT. (See 'Long-term health care maintenance' above.)
●Outcome – Surgical correction has resulted in excellent long-term survival, particularly for patients who are operated on at a young age, among whom survival is >90 percent 25 years after repair. Arrhythmia and heart failure leading to sudden cardiac death (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 (PVR). In addition, patients with TOF are at risk for long-term neurodevelopmental impairment. (See 'Long-term outcomes' above and 'Sudden cardiac death' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas Graham Jr, MD, who contributed to an earlier version of this topic review.
