Version May 2024
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 long-term management of complications.
The long-term complications and follow-up after TOF repair are discussed here. Other related topics include:
●(See "Tetralogy of Fallot (TOF): Management and outcome".)
●(See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)
●(See "Pulmonic regurgitation".)
●(See "Transcatheter pulmonary valve implantation".)
SURGICAL REPAIR
Repair in infancy — In the modern era, most patients with TOF undergo primary intracardiac repair in infancy (figure 2), typically before six months of age. Historically, TOF repair was performed in two staged procedures: a palliative shunt in early infancy followed by intracardiac repair later in childhood. Primary intracardiac repair has largely replaced the staged approach.
Additional details about surgical repair are provided separately. (See "Tetralogy of Fallot (TOF): Management and outcome", section on 'Surgical repair'.)
Repair in adulthood — Although it is now a rare occurrence, TOF remains the most common unrepaired cyanotic congenital heart disease defect in adults. Complete repair is feasible in adult patients and may result in improved function. However, there is an increased operative risk compared with younger patients.
Pulmonary valve replacement (PVR) is commonly required in adults undergoing TOF repair. Adults with unoperated TOF and prior palliative surgery commonly have severe RV hypertrophy and RV diastolic dysfunction and, therefore, tolerate severe pulmonary regurgitation poorly. Late repair can be complicated by previous palliative surgery as this increases operative complexity.
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) [1]. In the 10 patients who received a transannular patch, four required reoperation for PVR due to poorly tolerated pulmonary regurgitation. Approximately one-half of 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 five 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 [2,3].
LONG-TERM FOLLOW-UP — Patients who have undergone surgical repair of TOF require long-term follow-up with a cardiologist with expertise in congenital heart disease. Patients are at risk for long-term complications after surgery, including chronic pulmonary regurgitation, RV dysfunction, residual RV outflow tract (RVOT) obstruction, aortic root and valve dilation, arrhythmias, and sudden cardiac death (SCD) (table 2). (See 'Long-term complications' below.)
Care is focused on identifying, managing, and preventing these long-term sequelae.
Routine visits — Routine follow-up visits should occur at least annually, with a focused history, physical examination, and testing [4,5].
The history and physical examination focus on the patient's cardiac status, including:
●Episodes of palpitations, dizziness, or syncope, which may suggest an underlying arrhythmia.
●Symptoms (eg, dyspnea or decreased exercise tolerance) and signs of heart failure (eg, jugular venous distension, pulmonary congestion, peripheral edema, and hepatomegaly), which may be caused by valve dysfunction, shunt lesions, arrhythmias, and/or left or right ventricular dysfunction.
●Murmurs on cardiac auscultation may suggest pulmonary, tricuspid, or aortic valve regurgitation, or pulmonary or branch pulmonary artery (PA) stenosis.
Tests — The following tests are performed routinely in patients who have undergone repair of TOF. The frequency of testing varies depending on the patient's age, type of repair, symptoms, or ongoing cardiac issues (such as arrhythmias, RV dilation, or RVOT obstruction) [4,6] (table 3). Additional testing is performed as needed when new symptoms or signs develop.
●Echocardiography is recommended annually until the age of 10 years and every six months to two years through adulthood depending upon the patient's physiologic stage [4,6]. (See 'Physiologic stage' below.)
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 (LV) size, function, and wall motion
•Detect aortic root dilation and/or aortic valve insufficiency
●Electrocardiography (ECG) is performed at least once annually to assess cardiac rhythm and to evaluate QRS duration, which, if prolonged, is a risk factor for ventricular tachycardia (VT). (See 'Arrhythmias and sudden cardiac death' below.)
●Ambulatory ECG monitoring can be considered every one to two years for individuals with physiologic stage C or stage D. (See "Ambulatory ECG monitoring".)
●CMR – Advanced cardiac imaging, generally with cardiovascular magnetic resonance (CMR), is an essential component of the postoperative assessment of patients with TOF and is the gold standard for assessment of chamber sizes and ventricular performance. CMR is generally performed in adolescents and adults with repaired TOF every one to three years, depending on the clinical concerns [4]. Annual CMR is suggested for patients with any of the following findings [7]:
•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 [RVEF] <38 percent or >6 percent decrease in RVEF between studies)
Measurements of RV size and performance are important in determining the need for and timing of pulmonary valve replacement (PVR).
Assessment of all levels of the RVOT, including the branch PAs, is possible with CMR, 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.
●Cardiac CT – For patients in whom CMR is not an option (eg, due to an implanted CMR-incompatible pacemaker or implantable cardioverter-defibrillator [ICD]), cardiac computed tomography (CT) is performed to evaluate ventricular volumes and function. When using cardiac CT, the benefit of routine imaging is weighed against the risk of radiation exposure. (See "Clinical utility of cardiovascular magnetic resonance imaging".)
In addition, cardiac CT is preferred over CMR for patients who are being considered for PVR, since cardiac CT is required to evaluate candidacy for self-expanding transcatheter pulmonary valves (Harmony and Alterra). CT also provides important information for patients being considered for reoperation, including assessment of the coronary arteries and reentry planning. (See "Transcatheter pulmonary valve implantation".)
●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 performed in individuals when transcatheter intervention is being considered. Additional indications include assessment of hemodynamics to help guide therapy for patients with advanced heart failure or pulmonary hypertension and for those undergoing pretransplant evaluation. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)
Preoperative coronary artery assessment with CT or angiography is routinely performed in adults undergoing evaluation for intervention.
●Electrophysiologic study with mapping is performed in patients who are at risk for VT. (See 'Indications for EPS' below.)
Physiologic stage — The physiologic stage is categorized as follows (patients are classified based upon the highest [most severe] relevant physiologic feature) [4]:
●Stage A
•New York Heart Association (NYHA) class I symptoms (table 1)
•No hemodynamic or anatomic sequelae
•No arrhythmias
•Normal exercise capacity
•Normal renal/hepatic/pulmonary function
●Stage B
•NYHA class II symptoms (table 1)
•Mild hemodynamic sequelae (mild aortic enlargement, mild ventricular enlargement, mild ventricular dysfunction)
•Mild valvular disease
•Trivial or small shunt (not hemodynamically significant)
•Arrhythmia not requiring treatment
•Abnormal objective cardiac limitation to exercise
●Stage C
•NYHA class III symptoms (table 1)
•Significant (moderate or greater) valvular disease
•Moderate or greater ventricular dysfunction (systemic, pulmonic, or both)
•Moderate aortic enlargement
•Venous or arterial stenosis
•Mild or moderate hypoxemia/cyanosis
•Hemodynamically significant shunt
•Arrhythmias controlled with treatment
•Pulmonary hypertension (less than severe)
•End-organ dysfunction responsive to therapy
●Stage D
•NYHA class IV symptoms (table 1)
•Severe aortic enlargement
•Arrhythmias refractory to treatment
•Severe hypoxemia (almost always associated with cyanosis)
•Severe pulmonary hypertension
•Eisenmenger syndrome
•Refractory end-organ dysfunction
LONG-TERM COMPLICATIONS — Long-term complications after TOF repair include pulmonary regurgitation with associated RV enlargement, residual RV outflow tract (RVOT) obstruction, RV dysfunction, aortic root dilation and aortic valve insufficiency, arrhythmias including atrial tachycardia and VT, endocarditis, and SCD (table 2) [8-10].
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) [10-12]. Patients who have undergone repair with a transannular patch (figure 2) are at particularly high risk of needing reoperation [8]. (See 'Pulmonary valve replacement (PVR)' below.)
Chronic pulmonary regurgitation — Intracardiac repair with a transannular RVOT patch results in obligate chronic severe pulmonary regurgitation. Pulmonary regurgitation 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 regurgitation may vary depending on surgical approach and on the presence or absence of associated PA stenosis. Long-standing severe pulmonary regurgitation causes RV volume overload with often progressive RV enlargement [13,14]. This may be associated with increasing tricuspid regurgitation, further contributing to RV enlargement.
PVR is often necessary in patients with repaired TOF to restore pulmonary valve competence and improve RV function, as discussed in detail below. (See 'Pulmonary valve replacement (PVR)' below.)
Right ventricular dysfunction — Patients with repaired TOF are at risk for RV systolic and diastolic dysfunction [15]. Patients with RV volume and/or pressure overload are at risk for progressive adverse RV remodeling and RV dysfunction, associated with decreased exercise tolerance, right heart failure, and arrhythmias (ie, VT, SCD, atrial flutter, and atrial fibrillation). As discussed below, the goal of PVR is to improve RV remodeling before RV dysfunction and associated complications develop. (See 'Pulmonary valve replacement (PVR)' below.)
Left ventricular dysfunction — Patients with repaired TOF are also at risk for LV systolic and diastolic dysfunction [15]. The decline in RV function can also lead to LV dysfunction due to septal shift and ventricular/ventricular interaction [13,16,17].
Residual RVOT obstruction — 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 (most commonly, left PA stenosis in the region of ductal insertion) [18]. Mild obstruction is usually well tolerated, but severe obstruction may require reoperation or catheter-based intervention (transcatheter pulmonary valve implantation [TPVI]). Relief of PA stenosis by balloon dilation or stenting may be necessary prior to PVR or TPVI [19]. (See "Transcatheter pulmonary valve implantation", section on 'Conduit preparation and prestenting'.)
Aortic root 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 [20-22]; 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 [21,22]. Moderate to severe aortic valve regurgitation was observed in 3.5 percent of patients [22]. Aortic valve repair or replacement was performed in 1 to 2 percent or patients and another 1 to 2 percent underwent aortic root replacement. No patients had aortic dissection and there were no deaths due to aortic disease.
Endocarditis — Patients with repaired TOF are at increased risk of infective endocarditis (IE) [23]. Factors predisposing to IE among patients with repaired TOF include the presence of a prosthetic valve as well as the presence of residual defects at or adjacent to the site of prosthetic material. Among patients with surgical or transcatheter bioprosthetic pulmonary valves, the risk of endocarditis is highest among those with bovine jugular vein valves. This is discussed in greater detail separately. (See "Transcatheter pulmonary valve implantation", section on 'Endocarditis'.)
Measures to prevent IE are discussed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Arrhythmias and sudden cardiac death — Following surgical repair for TOF, patients are at risk of atrial tachyarrhythmias (ATs), ventricular arrhythmias, and SCD [6,24].
●Atrial tachyarrhythmias – The prevalence of ATs among adult patients with repaired TOF is approximately 20 percent; the risk increases considerably after age 45 years [25,26]. Initially, typical and atypical atrial flutter predominate; later, atrial fibrillation becomes increasingly prevalent.
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.
Risk factors for ATs include:
•For any AT – Increasing number of cardiac operations [25] and older age at repair [24].
•Atrial fibrillation/flutter – Left atrial dilation, lower LV ejection fraction, and tricuspid regurgitation [24,25].
•Intraatrial reentrant tachycardia – Right atrial enlargement and hypertension [25].
Additional details about the risk of ATs in the adult CHD population are provided separately. (See "Atrial arrhythmias (including AV block) in congenital heart disease".)
●Ventricular tachycardia – The prevalence of ventricular arrhythmias among adult patients with repaired TOF is approximately 15 percent [25,26].
Risk factors for VT in this population include increasing number of cardiac operations [25], LV systolic and diastolic dysfunction [25], pulmonary regurgitation [24,27], prolonged QRS duration [24,25], and older age at repair [2,3]. The risk of VT generally increases over time.
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 [28].
Monomorphic VT in TOF is usually dependent upon slow conduction within one of these isthmuses, identifiable either by direct activation mapping during VT or characterization of conduction properties within the isthmus. By this approach, VT can 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 [29]. Indications for electrophysiologic study (EPS) and ablation are discussed in greater detail below. (See 'Indications for EPS' below and 'Ablation' below.)
Although pulmonary valve regurgitation and RV dilation are associated with VT, the risk of VT is not eliminated with PVR [30,31]. Because transcatheter PVR may limit later access to potential ablation sites, many centers (including our own) perform EPS prior to PVR, as discussed below. (See 'Indications for EPS' below.)
●Sudden cardiac death – The risk of SCD in adults with repaired TOF is approximately 2 to 7 percent over 10 years [24,32-35]. In a study that included 869 adult patients with repaired TOF who were followed for a median of nine years, SCD occurred in 6 percent (and annual risk of 0.7 percent per year) [34]. The majority of SCD is presumed to be due to ventricular arrhythmia [36-38].
In addition to inducible VT on EPS, other reported risk factors for SCD and/or VT include [4,39-41]:
•Prolonged QRS (eg, QRS duration >180 ms)
•Older age at the time of repair
•Previous palliative shunt
•Higher number of thoracotomies
•RV dilation
•Ventricular dysfunction
•History of atrial arrhythmias
LONG-TERM MANAGEMENT ISSUES
Pulmonary valve replacement (PVR) — PVR is often necessary in patients with repaired TOF to restore pulmonary valve competence and improve RV function [42-46].
Indications — The optimal criteria for PVR in patients with repaired TOF are uncertain; various criteria have been proposed (table 4) [4,5,47,48]. Most experts agree that PVR is indicated in patients with moderate or severe pulmonary regurgitation (typically defined as regurgitant fraction >25 percent on CMR imaging) associated with any of the following [4,5,48]:
●Cardiovascular symptoms that are not otherwise explained.
●RV enlargement (typically defined by quantitative CMR measurements, including RV end-diastolic volume index [RVEDVi] ≥160 mL/m2 and/or RV end-systolic volume index [RVESVi] ≥80 mL/m2).
●RV systolic dysfunction.
●Reduced exercise capacity.
●Ventricular arrhythmias attributable to the right heart enlargement/dysfunction from pulmonary regurgitation.
However, the specific thresholds vary somewhat between different resources, as highlighted in the table (table 4). Ideally, PVR should be performed before RV dysfunction develops.
The evidence supporting use of these parameters and thresholds in determining the timing of PVR comes from observational studies of patients with repaired TOF who did or did not undergo PVR [46,47,49-55]. In a retrospective study from the INDICATOR database that included 1143 patients with repaired TOF who had CMR RV volumetric data available, 540 patients (47 percent) underwent PVR at a median of four months after CMR [47]. During median follow-up of eight years, 5 percent of the cohort died and 2 percent experienced resuscitated cardiac arrest or sustained VT. In a propensity score adjusted analysis, PVR was associated with lower risk of death, cardiac arrest, or sustained VT (hazard ratio 0.41, 95% CI 0.21-0.81). In a subgroup analysis exploring the effect of PVR in patients who did versus did not meet explicit criteria (as detailed in the first two columns of the table (table 4)), PVR was associated with lower risk of adverse outcome among patients who met criteria but not among those who did not meet criteria.
Following PVR, RV volumes decrease even in those with marked RV dilation [46,51-54]. However, patients with RVEDVi >160 to 170 mL/m2 or RVESVi >80 to 85 mL/m2 are unlikely to achieve restoration of normal RV volume [49,51-53]. A meta-analysis including 48 studies with a total of 3118 patients found that while greater pre-PVR RVEDVi was associated with greater reductions in RVEDVi and RVESVi post-PVR, greater pre-PVR RVEDVi was associated with lesser improvement in symptoms and functional class post-PVR [46].
Although aerobic exercise capacity typically improves substantially after PVR, studies have shown that patients who undergo PVR late in the disease process do not demonstrate improvement in RV function and exercise capacity [55,56]. A study of 25 adults with TOF undergoing PVR found that preoperative RVEF <40 percent was associated with reduced likelihood (13 versus 50 percent) of attaining an RVEF ≥40 percent at a mean of 28 months post PVR [55].
Pre-PVR evaluation — For patients who meet criteria for PVR, preprocedural evaluation generally includes the following:
●Imaging with echocardiography, CMR, and/or cardiac CT. Preprocedural imaging with cardiac CT is required to evaluate candidacy for self-expanding transcatheter pulmonary valves (Harmony and Alterra). (See "Transcatheter pulmonary valve implantation", section on 'TPV devices'.)
●Electrophysiologic study (EPS). (See 'Patients undergoing PVR' below.)
Surgical PVR — Outcomes following surgical PVR in patients with repaired TOF are discussed below. (See 'Comparative data' below.)
Additional details about surgical PVR are provided separately. (See "Pulmonic regurgitation", section on 'Surgical'.)
Transcatheter PVI (TPVI) — TPVI is an alternative to surgical PVR that is used in right ventricular to pulmonary artery conduits or native right ventricular outflow tracts (RVOT) with severe RVOT obstruction or severe pulmonary regurgitation [57-61]. Data comparing surgical PVR and TPVI in patients with repaired TOF are discussed below. (See 'Comparative data' below.)
Additional details regarding TPVR, including approved devices, complications (including risk of endocarditis), and need for reintervention, are discussed separately. (See "Transcatheter pulmonary valve implantation".)
Comparative data — Data directly comparing surgical PVR with TPVR in patients with TOF are limited to observational (mostly retrospective) studies [62-64]. Based on the available reports, long-term outcomes appear to be comparable.
In a meta-analysis of 11 observational studies (4364 patients), TPVR was associated with lower in-hospital mortality and shorter duration of hospitalization compared with surgical PVR, but reintervention rates and risk of infective endocarditis (IE) were higher with TPVR [64]. However, patients with repaired TOF accounted for only a subset of the study population in these studies, as many patients had other causes of pulmonary valve disease. In a multicenter retrospective study limited to patients with repaired TOF who underwent TPVR (n = 191) or surgical PVR (n = 382) from 2010 through 2016, in-hospital mortality was similar in both groups (1 percent each) as was the rate of procedure-related complications; however, hospital length of stay was shorter in the TPVR group (median one versus five days) [62].
Long-term outcomes after surgical and TPVR appear to be generally comparable:
●Outcomes after surgical PVR – In a meta-analysis of 15 observational studies including 2765 patients with TOF, overall survival following surgical PVR was 97 percent at five years and 94 percent at 10 years of follow-up [54]. Reintervention rates at five and 10 years were approximately 4 and 17 percent, respectively [54].
●Outcomes after TPVR – In a large multicenter study of 2476 patients who underwent TPVR (the underlying diagnosis was TOF in 55 percent), survival at eight years after the procedure was 91.1 percent [65]. Independent risk factors for mortality identified through multivariable analysis included age at the time of TPVR, concomitant prosthetic valve in another position, and presence of a transvenous pacemaker/defibrillator. The reintervention rate at eight years was 25 percent [65].
With both procedures, degeneration of the valve tissue can be expected over time. CMR data evaluating patients with repaired TOF who have undergone surgical PVR or TPVR demonstrated that the favorable RV remodeling noted initially after valve replacement deteriorated over 7 to 10 years in many of the patients, due to deterioration of the prosthesis [66]. 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 [67].
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. Mechanical prosthetic valves appear to be safe in this population [68].
Management of VT and prevention of SCD — VT and SCD are important causes of mortality after intracardiac repair of TOF. Identifying patients at risk for VT and SCD and providing an effective intervention (eg, ablation or ICD implantation) could reduce long-term mortality. However, a reliable risk stratification schema is lacking in this patient population.
Indications for EPS — EPS with programmed ventricular stimulation aids in the assessment for VT risk in patients with TOF and may be combined with radiofrequency ablation when a suitable VT substrate is identified.
Individual risk factors — EPS with ventricular stimulation is appropriate for patients with repaired TOF with one or more of the following symptoms of VT or risk factors for SCD or inducible VT:
●Symptoms that may be caused by VT include unexplained syncope and sustained palpitations [69].
●VT (symptomatic or asymptomatic) [4]. This includes recurrent VT resulting in repeated ICD shocks in patients with repaired TOF in whom EPS may identify a potential site for ablation.
●Some clinicians include RV dysfunction and extensive RV scarring as risk factors for VT that should prompt EPS [4].
●QRS duration ≥180 ms is a longstanding criterion [4,24], although a later report found that QRS fragmentation was a superior predictor of mortality in patients with TOF [70].
●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 and a history of atrial arrhythmias is a risk factor for inducible VT [49].
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 [71]. 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 CMR findings may correlate with electroanatomic mapping [72,73]. 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.
SCD risk scores — Some centers use the PREVENTION-ACHD risk score to identify adults with congenital heart disease (ACHD, including those with TOF) at risk for SCD [74,75]. The PREVENTION-ACHD risk score model estimates risk of SCD by assigning one point to each of the following risk factors:
●Coronary artery disease
●Heart failure symptoms (New York Heart Association [NYHA] class II or III)
●Supraventricular tachycardia
●Systemic ventricular systolic dysfunction (LVEF <40 percent)
●Impaired subpulmonic ventricular function (RVEF <40 percent)
●QRS duration ≥ 120 ms
●QT dispersion ≥70 ms
For adults with TOF, the presence of ≥3 risk factors is associated with an annual risk of SCD of 3 to 4 percent [75,76]. A study including 783 patients with ACHD (18 percent with TOF), the risk score model had a sensitivity of 50 percent and a specificity of 93 percent for SCD or VT/ventricular fibrillation in two years [75]. The risk score model was more sensitive than ICD indications in the 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society expert consensus statement on arrhythmias in ACHD (which had sensitivity of 25 percent and specificity of 98 percent) [69,75].
Patients undergoing PVR
●Prior to PVR – At many centers, including ours, EPS is performed in all patients undergoing PVR [49,74,77,78]. However, this practice is not standardized, and some centers perform EPS only in selected patients with TOF prior to PVR. Performing EPS prior to the PVR procedure may identify the responsible substrate, which can then be addressed either with radiofrequency ablation at the time of EPS or with intraoperative cryoablation at the time of surgery [30]. This approach is consistent with the European Society of Cardiology guidelines for management of ACHD [5]. The utility of this approach is debated but favored in many institutions experienced with VT ablation in this population. The rationale is based on the concern that the structural support of the prosthetic valve may block access to important anatomic isthmuses in the event of future VT.
A prospective multicenter study enrolled 120 patients with TOF who underwent EPS with programmed ventricular stimulation prior to PVR [49]. When the critical isthmus was identified, it was most commonly (90 percent) located between the ventricular septal defect patch and pulmonary annulus. The independent predictors of inducible VT were history of atrial arrhythmia and pulmonary annulus diameter >26 mm. EPS led to a change in management in 23 cases (19.2 percent): 18 underwent catheter ablation, three surgical cryoablation during PVR, and nine ICD implantation. Repeat PVR at a mean of five months after PVR was negative in eight of nine patients. No patient experienced sustained ventricular arrhythmia during 13 months of follow-up.
●Post-PVR – For patients known to have VT prior to PVR or considered to be at high risk based upon a positive EPS, EPS testing should be repeated after PVR. If there is persistence of inducible VT, management options include radiofrequency ablation and/or placement of an ICD [79]. (See 'Ablation' below and 'ICD placement' below.)
Ablation — When a defined substrate can be targeted, catheter or surgical ablation is a reasonable treatment option [4,30,80-85]. As an example, in a 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 cryoablation at the time of PVR in eight patients [86]. 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).
Follow-up EPS should be considered in patients undergoing catheter ablation or surgical ablation.
Catheter ablation — The role of EPS guided catheter ablation was illustrated by 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 [81]. 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".)
Intraoperative cryoablation — For patients undergoing surgical PVR, cryoablation of identifiable isthmuses can be performed intraoperatively. The additional risk associated with adding this procedure to PVR surgery is modest and it has the benefit of preemptively eliminating these areas of abnormal conduction that predispose to VT [30,85]. Preoperative mapping is generally warranted to define the precise VT substrate since the isthmus may not be reliably associated with the ventriculotomy scar itself [29]. (See 'Indications for EPS' above.)
In a cohort of 205 adult patients undergoing PVR, surgical cryoablation was performed in 22 patients based upon risk factors or prior VT [30]. Over a median follow-up of 6.7 years, VT or SCD occurred in 10 percent of patients who did not undergo cryoablation compared with 5 percent (1 of 22) of patients who underwent cryoablation.
ICD placement — Standard recommendations for ICD placement apply to patients at high risk for ventricular arrhythmias, including:
●Secondary prevention for those with documented sustained VT, ventricular fibrillation or prior episode of resuscitated SCD (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)
●Primary prevention for those with heart failure (NYHA functional class II or higher) and LVEF ≤35 percent on optimized medical therapy. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)
For patients with repaired TOF and inducible sustained VT that is hemodynamically unstable or otherwise not amenable to ablation, we suggest ICD implantation [4,87-89].
Indications for EPS are discussed above. (See 'Indications for EPS' above.)
Outcomes following ICD placement were described in two retrospective studies including a total of 286 adult patients with TOF who underwent ICD implantation for either primary or secondary prevention [87,90].
●During median follow-up of four to seven years, approximately 30 to 40 percent of patients received at least one appropriate and effective ICD discharge. The rate was slightly lower in patients who had the ICD placed for primary compared with secondary prevention (7 to 8 percent per year versus 10 to 12 percent per year, respectively). Factors associated with increased likelihood of receiving appropriate ICD discharges included higher number of SCD risk factors, elevated LV end-diastolic pressure, nonsustained VT, and QRS fragmentation on ECG.
●Approximately 30 to 40 percent of patients experienced at least one ICD-associated complication, including periprocedural complications (5 to 6 percent); inappropriate shocks (20 to 25 percent); lead-related complications (20 percent); and generator-related complications such as pocket infection, pain, or malfunction (6 to 10 percent). There were four arrhythmic deaths (1.4 percent), and three additional patients died due to SCD without tachyarrhythmias detected on ICD interrogation (presumed to be due to electromechanical dissociation).
Prevention of endocarditis — To reduce the risk of endocarditis, patients with TOF should maintain oral hygiene and receive timely treatment of infections. Patients with TOF may require antibiotic prophylaxis before certain dental or oral procedures to reduce the risk of IE. Antibiotic prophylaxis is recommended during the first six months after the corrective surgery or device or stent implantation. Prophylactic therapy is also recommended in patients who have prosthetic heart valves or if there are residual defects at the site 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".)
PREGNANCY — Pregnancy is not recommended in patients with unrepaired TOF [4]. For individuals with repaired TOF who do not have severe hemodynamic abnormalities, pregnancy outcomes are generally good [26,91-94]. A comprehensive cardiovascular evaluation by a congenital cardiac specialist is recommended prior to pregnancy to confirm there are no cardiovascular findings that should be 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 [95]:
●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 congenital heart disease (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 [4]. Approximately 15 percent of patients with TOF and other conotruncal defects have chromosome 22q11.2 microdeletion [96]. 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 [4]. (See "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Advanced fetal cardiac evaluation'.)
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 congenital heart disease (CHD), including TOF [80]. 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 3).
●Patients with repaired TOF may be considered for participation in moderate- to high-intensity sports (figure 3) if they do not have evidence of clinically significant right or left ventricular dysfunction (ejection fraction >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".)
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 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
●Surgical repair – In the modern era, most patients with tetralogy of Fallot (TOF) (figure 1) undergo primary intracardiac repair in infancy (figure 2). Although it is now a rare occurrence, TOF remains the most common cyanotic congenital heart disease (CHD) defect to reach adulthood without surgical repair. Complete repair is feasible in adult patients and may result in improved function. However, operative risk is high. (See 'Surgical repair' above.)
●Long-term follow-up – Patient who have undergone surgical repair of TOF require long-term follow-up with a cardiologist with expertise in CHD. Routine follow-up visits should occur at least annually, with a focused history, physical examination, and cardiac testing at regular intervals, as summarized in the table (table 2). (See 'Long-term follow-up' above.)
●Long-term complications – Patients who have undergone intracardiac repair for TOF are at risk for chronic postoperative complications, including (table 2) (see 'Long-term complications' above):
•Pulmonary regurgitation with associated right ventricular (RV) enlargement (see 'Chronic pulmonary regurgitation' above)
•Residual RV outflow tract (RVOT) obstruction (see 'Residual RVOT obstruction' above)
•RV dysfunction (see 'Right ventricular dysfunction' above)
•Aortic root dilation (see 'Aortic root dilation' above)
•Infective endocarditis (IE) (see 'Endocarditis' above)
•Arrhythmias, including atrial tachyarrhythmias (ATs), ventricular tachycardia (VT), and sudden cardiac death (SCD) (see 'Arrhythmias and sudden cardiac death' above)
●Long-term management issues
•Pulmonary valve replacement (PVR) – PVR is often necessary in patients with repaired TOF to restore pulmonary valve competence and improve RV function. Ideally, PVR is performed before severe RV dysfunction develops; however, the optimal timing remains uncertain. We suggest PVR in patients with moderate or severe pulmonary regurgitation associated with any of the following (Grade 2C) (see 'Indications' above):
-Cardiovascular symptoms that are not otherwise explained
-RV enlargement
-RV systolic dysfunction
-Reduced exercise capacity
-Ventricular arrhythmias attributable to the right heart enlargement/dysfunction from pulmonary regurgitation
Specific thresholds used to define these criteria are detailed in the table (table 4).
PVR can be performed surgically or with a transcatheter procedure (TPVR). Long-term outcomes appear to be comparable with both procedures. (See 'Surgical PVR' above and 'Transcatheter PVI (TPVI)' above.)
•Management of arrhythmias and prevention of SCD – Arrhythmias and SCD are important causes of mortality after intracardiac repair of TOF.
-Atrial arrhythmias – Management of atrial arrhythmias is discussed separately. (See "Atrial arrhythmias (including AV block) in congenital heart disease", section on 'Management'.)
-VT – Patients with documented VT or with risk factors for VT should undergo electrophysiology study (EPS) with ventricular stimulation. If a defined substrate is identified, we suggest catheter ablation (Grade 2C). Alternatively, for patients undergoing surgical PVR, cryoablation of identifiable isthmuses can be performed intraoperatively. (See 'Indications for EPS' above and 'Catheter ablation' above and 'Intraoperative cryoablation' above.)
Standard recommendations for implantable cardioverter-defibrillator (ICD) placement apply to patients at high risk for ventricular arrhythmias, including secondary prevention for those with documented sustained VT, ventricular fibrillation, or prior episode of resuscitated SCD and primary prevention for those with symptomatic ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤35 percent). This is discussed in greater detail separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)
For patients with TOF and inducible sustained VT that is hemodynamically unstable or otherwise not amenable to ablation, we suggest ICD implantation (Grade 2C).
•Endocarditis prophylaxis – Patients with TOF may require antibiotic prophylaxis before certain dental or oral procedures to reduce the risk of IE. 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".)
●Pregnancy – When possible, patients with TOF should have a comprehensive cardiovascular evaluation by a congenital cardiac specialist before pregnancy to confirm there are no cardiovascular findings that should be addressed before a pregnancy, or to suggest a pregnancy would be high risk and not advised. For individuals with repaired TOF who lack severe hemodynamic abnormalities, pregnancy outcomes are generally good for both the mother and infant. (See 'Pregnancy' above.)
●Sports participation – Recommendations regarding participation in competitive sports should be tailored to the individual and informed by a comprehensive evaluation by an experienced clinician. (See 'Sports participation' above and "Physical activity and exercise in patients with congenital heart disease".)
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