Developmental and Anatomic Aspects

Tetralogy of Fallot affects approximately 7.5 % of all children born with a congenital heart defect. It is characterized by subpulmonary stenosis, a subaortic ventricular septal defect, dextroposition of the aortic orifice, and right ventricular hypertrophy, the latter being a secondary feature to the volume and pressure overload of the ventricular septal defect and subpulmonary stenosis, respectively.

During normal development, the outlet portion of the heart needs to evolve from a single myocardial tube to a situation where the separated aorta and pulmonary trunk achieve their definitive positional relationship. This process requires proper septation of the outlet portion of the heart. Formation of the aortopulmonary septum (future outlet septum), orchestrated by neural crest cells, will result in separation of the common trunk into an aorta and pulmonary trunk. Asymmetrical, mainly subpulmonary myocardial contributions from the so-called second heart field will result in marked lengthening of the subpulmonary myocardium and will “push” the pulmonary trunk to its definitive position left anterior to the aorta.⁸ After proper development, the right ventricular outflow tract (RVOT) is characterized by the presence of a muscular subpulmonary infundibulum forming a circular muscular tube below the pulmonary valve. The posterior wall of the infundibulum, also known as the crista supraventricularis, is situated between the tricuspid valve and the pulmonary valve. The crista supraventricularis forms the summit of the ventriculo-infundibular fold (VIF), a fold of myocardium at the posterolateral wall of the RVOT, and extends toward the ventricular septum into the trabecula septomarginalis (Figure 102-1). The latter continues over the interventricular septum and contains the right bundle branch. The crista supraventricularis also encompasses the outlet septum (the muscular septum separating the aortic en pulmonary outlets), situated in between the ventriculo-infundibular fold and trabecula septomarginalis, which is small and not recognizable as a separate structure in the normal heart. In TOF, however, there is an anterior deviation of the outlet septum that, in contrast to normal, can be recognized as a separate structure, which is regarded as a pathognomonic feature of TOF (see Figure 102-1). The deviation of the outlet septum causes malalignment with the remainder of the ventricular septum, resulting in a subaortic, and in most cases perimembranous, ventricular septal defect. The deviation of the outlet septum also contributes to the subpulmonary stenosis. The amount of displacement and hypertrophy of the outlet septum determines the severity of the stenosis. The morphology of TOF encompasses a broad spectrum, with on the one end very slight malformations and cyanosis and on the other end severe forms of the disease with pulmonary atresia.

Type and Timing of Surgical Repair and Its Potential Relation to Risk Factors for Ventricular Arrhythmias

After the first intracardiac repair of TOF in 1954 by Lillehei in a 10 month-old boy, subsequent series of early surgical interventions reported a high perioperative mortality leading to a “two-stage repair” with a palliative shunt to augment pulmonary blood flow, followed by total repair later in childhood.

Total repair included (patch) closure of the perimembranous or muscular VSD and relief of the infundibular or valvular RVOT obstruction. This repair was initially performed through a vertical or transverse right ventriculotomy often combined with the use of an RVOT or a transannular patch to augment the restrictive RVOT or to relieve the stenosis of the pulmonary orifice. The malformation and type of repair are important determinants of potential reentrant tachycardia circuits, which is a common underlying mechanism of VT in repaired TOF.⁸ Areas of dense fibrosis owing to surgical incisions, but also patch material and the valve annuli, can form regions of conduction block that define reentry circuit borders and create intervening isthmuses of myocardial bundles that might contain the critical reentry circuit isthmus of a macroreentrant VT. Four anatomic isthmuses related to VT in repaired TOF have been identified⁹: isthmus 1 bordered by the tricuspid annulus and the scar or patch in the anterior RVOT, isthmus 2 between the pulmonary annulus and the RV free wall incision or RVOT patch sparing the pulmonary valve annulus, isthmus 3 between the pulmonary annulus and the VSD patch or septal scar, and isthmus 4 between the VSD patch or septal scar and the tricuspid annulus in patients with muscular VSDs (see Figure 102-1).

The right ventriculotomy and the frequent use of a transannular patch with consecutive pulmonary regurgitation and chronic volume overload often resulted in RV dilatation and dysfunction, which is associated with VT and SCD in the long term (Table 102-1). Consequently, a combined transatrial-transpulmonary approach has been introduced. Currently, patch augmentation is avoided or usually limited to the pulmonary annulus whenever possible. This approach does not only positively affect RV function but can also prevent the anatomic isthmuses 1 and 2.

Reentrant tachycardias are promoted by slow conduction. Interstitial fibrosis owing to longstanding cyanosis and pressure overload, functionally prolongs the pathway for impulse propagation and can provide the substrate for slow conduction. In addition, cell-to-cell coupling can be diminished because of decreased gap junction density and altered connexin expression and distribution, as observed in clinical and experimental cardiomyopathies also contributing to slow conduction.

Myocardial histopathologic changes, in particular interstitial fibrosis of the muscular tissue of the crista supraventricularis, are more pronounced in patients who were operated at older age, specifically beyond the age of 4 years, and are thus subjected to long standing cyanosis (SaO₂ < 80%) and higher end-diastolic RV pressure (>12 mm Hg).¹⁰ The clinical gold standard to detect ventricular fibrosis is late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). Myocardial LGE was present in both the RV and LV of adults after repair of TOF and was related to increased age, and adverse clinical effects such as ventricular dysfunction and specifically RV LGE were associated with atrial and ventricular arrhythmias.¹¹

Histopathologic changes can also contribute to the occurrence of complex ventricular ectopy, which has been considered a risk factor for fatal ventricular arrhythmias (VA). In particular, older age at repair has been associated with a higher grade of ventricular ectopy. Only 11% of patients in whom repair was performed between the ages of 4 and 15 years showed complex ectopy on Holter monitoring 6 to 12 months after operation, compared with 39.4% of patients who underwent surgery beyond the age of 15 years.¹⁰ The age dependency of the occurrence of complex ventricular ectopy could also be demonstrated in uncorrected patients. No significant ventricular ectopy (defined as Lown ≥ 2, <30 uniform PVCs/h) was observed in patients 0 to 7 years old. In contrast, 58% of patients 16 years or older had complex ectopy, with 21% having runs of nonsustained VT. Of interest in corrected patients, the relation of complex ventricular ectopy and time of repair persisted and was independent of the duration of follow-up or of the postoperative hemodynamic status.¹² Although a higher grade of ectopy and nonsustained VT have been associated with VT inducibility, inconsistent data exist regarding their association with SCD. Accordingly, treatment of asymptomatic complex ventricular ectopy is not recommended.¹³ Primary repair in infancy before the age of 18 months is common practice since the early 90s and can be performed with low perioperative mortality. Avoiding long-standing prolonged hypoxemia and pressure overload can reduce the histopathologic changes and the substrate for slow conduction, complex ventricular ectopy, and fatal VA.

Despite early operation, progressive pulmonary regurgitation occurs in almost all patients after transannular patch repair and is an important reason for reintervention. Although often tolerated, pulmonary regurgitation ultimately leads to RV dilatation and dysfunction, which can be further aggravated by residual RVOT obstruction. Moderate to severe PR and abnormal RV hemodynamics in particular, and increased RV end-systolic pressure have been associated with VT and SCD. In addition, a wide QRS (>180 ms) and an increase in QRS duration have consistently been reported as risk factor for SMVT and SCD.⁵ In particular, RV dilatation but not restrictive RV physiology has been associated with QRS prolongation, referred to as mechanoelectrical interaction.¹⁴

Impairment of RV function and LV hemodynamics have important roles. A moderate to severe left ventricular systolic dysfunction—defined as ejection fraction (EF) of less than 39% and 20%, respectively—was also more common in patients with TOF and (aborted) SCD.¹⁵ In addition, an left ventricular end diastolic pressure (LVEDP) ≥ 12 mm Hg was a strong and independent predictor of appropriate ICD shocks in patients with TOF who received an ICD for primary prevention.¹⁶

Effect of Pulmonary Valve Replacement and Intraoperative Cryoablation on Ventricular Arrhythmias

In selected patients, a reduction in QRS duration after pulmonary valve replacement (PVR) was related to a reduction in RV EDV assessed by CMR, which further supports the occurrence of mechanoelectrical interaction.¹⁷ A QRS duration greater than 180 ms 6 months after PVR, or no reduction of the QRS duration postoperatively, were strong predictors of adverse events defined as all-cause mortality, reoperation for pulmonary regurgitation, heart failure or VT.¹⁸ In particular, patients with severely prolonged QRS duration that did not change postoperatively had the highest incidence of adverse events. Prolonged QRS duration can serve as one surrogate marker for the changes in mechanical forces that trigger changes on the cellular and subcellular level also known as mechanoelectrical coupling associated with arrhythmogenesis.

Despite the remarkable reduction of RV volumes and hemodynamic improvement of RV function after PVR,¹⁹ simply replacing the valve might not eliminate the substrate for reentrant ventricular tachycardias; reentry was the underlying mechanism of all VTs that were also associated with a QRS greater than 180 ms in one series.¹⁴ After a late PVR performed in 98 patients 20 ± 9 years SD after TOF repair, VT occurred in 11, and death occurred in 6 patients after a mean follow-up of 2.8 ± 4.3 years. The 5- and 10-year measures of freedom of the composite outcome of death and VT was 80% and 41%, which was not different from a control group (n = 77) matched for age, pulmonary regurgitation, RV dilatation, and QRS duration and who did not undergo PVR.²⁰ These data suggest that either PVR was performed too late, not leading to a favorable reverse remodeling despite a reduction in RV size, or VTs are the result of a fixed substrate not influenced by hemodynamic improvements. Of interest, five of seven patients who underwent PVR and concomitant (not further specified) intraoperative cryoablation experienced VT during follow-up. In contrast, map-guided intraoperative ablation was more effective to control VT recurrence. Of 44 patients with documented monomorphic sustained ventricular tachycardia (MSVT), 31 underwent cryoablation applied to the macroreentry site as assessed by combined endocardial and epicardial mapping during cardioplegic arrest. VT recurred in only three (10%) patients after ablation with a 96% freedom of VT after 7.5 years.²¹

Role of Programmed Electrical Stimulation

A positive programmed electrical stimulation (PES), usually defined as inducibility of a sustained monomorphic VT, provides an important tool to prove the presence of a substrate for reentrant VT, although VT based on triggered activity may also be inducible in the electrophysiology laboratory. Accordingly, only 16% of patients who had documented sustained VT were not inducible by PES.²²

Consequently, PES has also been used to identify patients with TOF who are at risk of potential fatal ventricular arrhythmias. Inducibility of sustained VT is high in patients with presyncope and complex PVCs on Holter monitoring and is more likely in patients repaired at older age and when PES is performed late after surgery.23,24 Importantly, inducibility strongly depends on the applied induction protocol; MSVT induction required three extrastimuli in 70% and isoproterenol in 11% of the patients in two series.^22,23 Using a complete PES protocol (two RV sites, 3 cycle lengths (CL), triples and isoproterenol) the diagnostic value (sensitivity, 77.4%; specificity, 79.5%) and the prognostic significance (relative risk, 5.0 for subsequent clinical VT or SCD) of PES in TOF patients is comparable with the postinfarct population.²² Of interest, the highest event rate (SCD, VT, or both) was observed in patients inducible for sustained polymorphic VT (SPVT). Although derived from a small number of patients, induction of SPVT may not be an unspecific finding and may reflect a different but potential fatal arrhythmogenic substrate.

Type of Ventricular Arrhythmias and the Underlying Substrate: Impact on Treatment

The majority of VA documented in TOF patients is monomorphic VT. The prevalence of SMVT was 14.2% in a recently conducted multicenter study including 556 TOF patients and was markedly increased after the age of 45. In contrast, in only 0.5% of the population VF could be documented.² The incidence of VF in TOF patients may be underestimated as patients in the cohort are survivors. However, in 121 TOF patients who have received an ICD for primary or secondary prevention, 81.5% of all appropriately delivered therapy was for monomorphic VT. Of importance, VTs were fast with a median heart rate of 213 bpm (182-264).¹⁶

There are no data available on the efficacy of antiarrhythmic drugs and only limited data on dosage and toxicity in different age groups. In general, anti-arrhythmic drugs initiated to prevent recurrence of reentrant VT in structural heart disease have disappointing efficacy and the use of anti-arrhythmic drugs is hampered by potentially serious side effects.

The feasibility of catheter ablation of VT in CHD with the majority performed in TOF patients has been reported (Table 102-2). In most of the earlier series and case reports, the targeted VTs were slow, hemodynamically tolerated, and therefore approachable by conventional mapping techniques, such as activation and entrainment mapping during ongoing VT. An intention to treat analysis was published by the group from the Boston Children’s Hospital.²⁵ In this study, acute ablation failure was 50% because of noninducibility, hemodynamic instability, or anatomic reasons. Two recently published studies used substrate mapping techniques to target all inducible and, in particular, fast and poorly tolerated VTs, which are common.

Using a noncontact mapping system consisting of a multielectrode balloon array that allows simultaneous acquisition of virtual unipolar electrograms, the activation sequence of 13 fast or nonsustained VTs in 10 patients could be obtained.²⁶ Eleven of the 13 induced VTs were due to macroreentrant circuits, whereas two were due to microreentrant circuits. The anatomic location of the isthmus could be identified in all patients and was successfully targeted by a linear radiofrequency (RF) lesion in eight patients. In two patients, RF delivery was withheld because of the proximity of the His bundle. An alternative approach applies point-by-point electroanatomic voltage and activation mapping during stable sinus rhythm to obtain a three-dimensional reconstruction of all potential isthmuses by identifying the anatomic boundaries (see Figure 102-1).⁹ Peak-to-peak bipolar electrogram amplitudes can be displayed color-coded and projected on a three-dimensional shell of the RV. Electrograms greater than 1.5 mV are considered normal voltage. At sites with amplitudes less than 0.5 mV, high output pacing (10 mA, 2 ms) can be performed to identify unexcitable tissue, which is consistent with patch material or surgical scars. Connecting the anatomic isthmuses by linear RF lesions has been highly effective to treat all VTs, and in particular poorly tolerated ones, with promising long-term results. In the largest series to date, reporting on VT ablation targeting anatomic isthmuses in 31 adults with CHD (81% TOF; mean VTCL of 298 ± 74 ms) total procedural success defined as noninducibility of any VT was achieved in 22 adults (71%). None of the patients in whom complete procedural success was achieved had recurrence of a monomorphic VT during 43 ± 28 months of follow-up, whereas one patient with poor RV function experienced appropriate ICD discharge for VF. These data suggest that macroreentrant VTs based on an anatomic substrate can be treated effectively with catheter ablation; however, other VA can occur in patients with impaired RV function.⁹

Of importance, inducibility of the clinical arrhythmia and hemodynamic tolerance is no longer a prerequisite for successful ablation. The association between anatomically defined isthmuses and macroreentrant VT might also be helpful to guide intraoperative ablation in patients who require reoperation for PV regurgitation.

Implantable Cardioverter Defibrillator

As discussed earlier, the risk of SCD in patients with surgically corrected TOF is estimated to be 1.2% to 1.8% 10 years after surgery and 2.5% 20 years after surgery. The SCD risk increases to 4% and 6%, respectively, 25 and 30 years after surgery. Several factors associated with SCD in patients with TOF have been identified (see Table 102-1); however, the prognostic value of each factor is limited. According to the AHA/ACC and ESC guidelines, an implantable cardioverter defibrillator (ICD) should be implanted in SCD survivors.^13,27 Furthermore, an ICD should be implanted in patients with ventricular arrhythmias after failed catheter ablation. ICD implantation can be considered in patients after unexplained syncope without a defined and reversible cause. However, if symptoms of presyncope of syncope are reported, an induction protocol for both VT and supraventricular tachycardias may be helpful. Prophylactic implantation of ICDs is still under debate, but could be considered in the presence of LV/RV dysfunction, extensive fibrosis, and a QRS greater than 180 ms and if VT is inducible during electrophysiological study.^13,27 In high-risk patients with TOF, ICD implantation has been shown to be effective for both primary and secondary prevention, with appropriate and effective shocks in more than 30% of patients.¹⁶ Of importance, more than 80% of the treated ventricular arrhythmias were monomorphic and fast VT (median heart rate, 212 beats/min), but 70% of the patients required ICD shocks to terminate the first arrhythmia. These fast VT are currently approachable by substrate-based ablation techniques, which should be considered in particular in patients with preserved RV and LV function. However, long-term efficacy data of catheter ablation of fast VT are lacking. Important device-related complications are inappropriate shocks, which were observed in 25% to 30% of all patients^16,28 (actuarial rate 5.8% of patients per year) and are often due to supraventricular arrhythmias and late lead-related complications occurring in 20%.¹⁶

Developmental and Anatomic Aspects

Transposition of the great arteries is the most common cyanotic heart disease in newborns, comprising 5% of all congenital heart diseases. It can occur isolated (simple TGA) or in association with other congenital malformations (complex TGA). In TGA, there is a concordant atrioventricular (AV) connection in combination with ventriculoarterial discordance, with the aorta connecting to the morphologic right ventricle, and the pulmonary trunk to the morphologic left ventricle. There is often a parallel course of the great arteries, with a right anterior position of the aorta with respect to the pulmonary orifice.²⁹ From a developmental point of view, the abnormal position of the great arteries in TGA might be related to a deficient lengthening of the outflow tract during development, for which contributions from the so-called second heart field are necessary.⁸

Complex TGA is most commonly associated with ventricular septal defects (in approximately 40%) and left ventricular outflow tract (LVOT) or RVOT obstruction. In cases with infundibular VSDs, the outlet septum can often be recognized as a separate structure. Obstruction of the RVOT and LVOT are usually caused by rightward deviation and leftward deviation of the outlet septum, respectively, and can become more pronounced by hypertrophy of the outlet septum. In addition, muscle bundles, subvalvular fibrous tissues, or abundant AV valve tissues can contribute to narrowing of the RVOT and LVOT.²⁹

Type and Timing of Surgical Repair and Its Potential Relation to Risk Factors for Ventricular Arrhythmias

Before the 1980s, most patients underwent a two-stage–repair surgical intervention. The Blalock-Hanlon atrial septectomy, introduced in 1950 and replaced by the Raskind balloon atrial septostomy after 1966, is usually performed acutely after birth. This is followed by an atrial switch operation—either the Senning or the Mustard procedure—within the first year of life. The Senning procedure, first performed in 1959, used the atrial septum to create a baffle to redirect the blood flow from the caval veins to the left ventricle. The Mustard procedure, introduced in 1964, used a baffle from pericardium or synthetic material.

Currently, most of the patients seen at the adult outpatient clinic have been treated with the atrial switch operation. SCD is the leading cause of late mortality and seems to be constant over time, with an estimated incidence of 4% ± 7% at 10 years and 9% ± 4% at 20 years of follow-up.³ In a retrospective study of 47 patients with sudden death (SCD; 13 aborted), the event occurred at a median age of 9.7 years (range, 0.3 to 32 years) and 7.9 years (range, 0.3 to 28.8 years) after surgery.³⁰

Of importance, more than 80% of these SCDs occurred during exercise, likely because of an inability to increase cardiac output as a response to the increased demand, leading to low output cardiac failure. The latter can be worsened by coexisting conditions such as baffle obstruction, pulmonary vein stenosis, or ventricular dysfunction.³⁰ Atrial arrhythmias that preceded SCD in 7% of the patients further impair AV transport and decrease RV filling. Right ventricular dysfunction may also lead to ventricular arrhythmia as a consequence of RV dilatation and tricuspid regurgitation, resulting in hemodynamic compromise and mechanoelectrical interaction (i.e., a relation of mechanical and electrical properties of the RV, due to which right ventricular dilation and life-threatening arrhythmias may occur.¹⁴ Ischemia of the systemic RV may further contribute to ventricular arrhythmogenesis.³¹ Late enhancement CMR studies have indicated the occurrence of myocardial fibrosis in the systemic right ventricle in patients after physiological correction, which may be relevant in the occurrence of ventricular arrhythmias.³²

Although risk stratification is generally limited, symptoms of arrhythmias and heart failure and documented atrial flutter or fibrillation have been identified as predictors of SCD in patients after a Mustard or Senning procedure.³⁰

The implication of supraventricular arrhythmias for the occurrence of ventricular arrhythmias is further supported by the observation that 50% of all appropriate ICD shocks in primary or secondary prevention ICD recipients were preceded by or coexisted with supraventricular tachycardia.³³ Risk factors as identified in patients with TOF are of limited value. Only 1 of 23 patients who received an ICD for primary prevention experienced appropriate ICD therapy. Implantation was prompted by presyncope in 48% of patients, nonsustained (ns) VT in 48%, QRS duration ≥ 180 ms in 30%, right ventricular ejection fraction (RVEF) ≤ 35% in 35%, and inducible VT in 30.4%.

However, in a single-center review of 149 adults, the combined endpoint of sustained VT and SD was more likely in patients with additional anatomic lesions, impaired RV function, NYHA class III or greater, and a QRS duration of 140 ms or greater.

Since 1975, anatomic correction with the arterial switch operation has become the treatment of choice. During this procedure, the aorta and pulmonary trunk are disconnected from their arterial roots (that will remain in their original position) and “switched” to connect to the proper ventricle. This approach not only reduces the incidence of postoperative atrial arrhythmias and sinus node dysfunction; it is also likely to reduce fatal ventricular arrhythmias as the left ventricle supports the systemic circulation. In complex cases of TGA, modification of these operations or other operation techniques may be necessary, such as the Rastelli operation for treatment of TGA with LVOT obstruction.

Role of Programmed Electrical Stimulation

There are few data regarding the role of PES in adult patients with TGA. In one series 17 patients underwent PES before ICD implantation (10 of 17 patients for primary prevention). Nine patients (6 of 9 primary prevention patients) were inducible, but with only three for monomorphic VT and six for polymorphic sustained VT. During follow-up, none of the inducible but three of the noninducible patients, all receiving implants after a spontaneous ventricular arrhythmia event, experienced appropriate ICD therapy. These data suggest that different substrates and underlying mechanisms occur in patients with TGA.

Type of Ventricular Arrhythmias and the Underlying Substrate: Effect on Treatment

The Senning and Mustard procedures result in physiological repair, after which the morphologic right ventricle supports the systemic circulation with the risk of right heart failure and related ventricular arrhythmias over time. Accordingly, more than 50% of all VAs prompting ICD therapy in TGA in patients receiving implants for primary or secondary prevention were polymorphic VT or VF.³³ Sustained monomorphic VT is relatively uncommon, with an estimated incidence rate of 0.5% per year.³

Simple TGA does not require surgical incisions of the ventricles or patch material, which has been associated with monomorphic VT in the TOF population. Surgical incisions or patch material are however necessary in complex TGA, which is usually defined as the additional presence of a VSD requiring patch closure or other lesions like outflow tract obstruction requiring surgical intervention.30,34 Surgical scars and patch material can serve as anatomic boundaries facilitating macroreentrant VT as in TOF (Figure 102-2). In an adult cohort of 149 patients in which 107 (72%) had simple transposition, sustained VT was documented in seven patients. Four of these seven had complex TGA. VT occurred in 9.5% of patients with complex TGA, but in only 2.8% of patients with simple TGA.³⁴ Sustained VT is rarely observed during childhood. The deterioration of RV function over time with electrical and structural remodeling, which is more often observed in complex TGA (42% vs. 2% at 20 years),³⁵ is likely to contribute to the late occurrence of VT and SD.

There are no specific data on medical treatment of VA in TGA, and only four case reports on catheter mapping and ablation of monomorphic VT, all of which were performed in patients with complex TGA (see Table 102-2). The underlying mechanism was reentry, and the critical reentrant circuit isthmus was located in an anatomic isthmus bordered by the VSD patch and the aortic valve in three patients, and in an area of septal transmural scar and at the aortic valve in one patient. In the latter patient, preprocedural imaging of the three-dimensional scar architecture by LGE CMR and its spatial relationship to the aortic valve identified the anatomic isthmus (see Figure 102-3). Integration of the CMR-derived anatomic information with the electroanatomic mapping data was applied to guide and facilitate ablation.³⁶ Substrate imaging and image integration should be considered in all patients with CHD with complex anatomy and surgical scars.³⁶

Implantable Cardioverter Defibrillator

The risk of SCD in TGA is reported to be 4% after 10 years and 9% after 20 years (5 to 8 per 1000 patient-years). In the majority of patients who have undergone an atrial switch operation, ventricular arrhythmias are the underlying cause of SCD. It is important to note that ventricular fibrillation can be preceded by atrial arrhythmias in a significant number of these patients.³³ Other reported risk factors for SCD are RV dysfunction, venous obstruction and a QRS duration of 140 ms or greater³⁴; however, specific criteria that prompt ICD implantation have not been defined. An ICD should be implanted after an SCD episode and can be considered in patients with unexplained syncope without defined and reversible cause.^13,27

In TGA patients after atrial switch, ICD implantation has been shown to be effective for secondary prevention. However, effectiveness of ICD implantation for primary prevention could not be demonstrated, and inducible VT on electrophysiological testing did not predict future events, suggesting that risk stratification is limited.³³ It is important to recognize that implantation of an ICD can be technically challenging because of the presence of intraatrial baffles and implantation of the lead in a morphological left ventricle. In addition, after ICD implantation the number of inappropriate shocks (6.6% per year) and late lead-related complications are high.^33,37

Left Ventricular Outflow Tract Obstruction

Despite surgical repair, aortic stenosis has the highest incidence of SCD (5.4 per 1000 patient- years).³ LVOT obstruction comprises a variable group of patients with obstruction at the subvalvular, valvular, or supravalvular level. Valvular stenosis, which constitutes the largest group in congenital heart disease patients, is usually attributable to a bicuspid aortic valve. Congenital cases of subvalvular aortic stenosis are usually the result of a subaortic valvular membrane. Supravalvular aortic stenosis is less common and is often associated with other congenital malformations or syndromes, such as Williams syndrome, or related to previous surgery (e.g., the suture site in the ascending aortic wall after arterial switch for TGA).

The risk of SD in patients with aortic stenosis seems time dependent. Etiologies of SD were variable and included arrhythmic SD (often in the presence of significant residual valve dysfunction), cerebral and coronary complications (often related to aortic valve endocarditis), and low cardiac output failure secondary to acute ventricular failure.³ Other suggested mechanisms for the high occurrence of sudden cardiac death in this group include ventricular dysfunction and ventricular hypertrophy. Deficient coronary perfusion during exercise can play a role in patients with unoperated severe aortic stenosis. In asymptomatic patients with aortic stenosis, QRS duration and morphology were independently associated with the risk of SCD.³⁸

Coarctation of the Aorta

The reported incidence of SCD in patients’ after repair of coarctation of the aorta is 1.3 per 1000 patient-years.³ Coarctation of the aorta can occur at different levels, but it is classically found at the so-called isthmus, just below the branching of the left subclavian artery. One third of patients have a bicuspid aortic valve. Even after surgical resection of the coarctation, patients can be remain prone to hypertension and concomitant left ventricular hypertrophy that can contribute to the increased incidence of SCD in this group.

Atrioventricular Septal Defect

In patients with atrioventricular septal defect (AVSD), the reported incidence of SCD is 0.9 per 1000 patient-years.³ AVSD is part of a broad morphologic spectrum that includes complete AVSD and partial AVSD. Extreme disbalance of the ventricles can result in hypoplastic right or left heart syndrome. AVSD can occur isolated and in association with other CHD, such as left ventricular outflow tract obstruction. AV conduction disorders can occur because of an abnormal position and morphology of the AV conduction system. Ventricular arrhythmias and SCD are less common and can be related to LVOT obstruction, the amount and duration of left AV valve regurgitation, the amount of ventricular disproportion, complete AV block, and the association with complex cardiac anomalies, although data are limited.

Congenitally Corrected Transposition of the Great Arteries

In ccTGA, there is discordance at both the atrioventricular and ventriculoarterial level. In the absence of atrial or ventricular septal defects or an open ductus arteriosus, patients will not exhibit shunting or cyanosis, and late complications of the disease are largely associated with the fact that the RV is the systemic ventricle, predisposing for right heart failure, and regurgitation of the often abnormal (Ebstein-like) tricuspid valve. Data on the occurrence of ventricular arrhythmias in this group are limited. Ventricular tachycardia and SCD can be related to ventricular dysfunction, AV valve regurgitation, or AV block. In a cross-sectional study examining the mode of death in patients with CHD, mortality in patients with ccTGA was 40% related to SCD.³⁹

Univentricular Hearts

Univentricular heart comprises a highly heterogenous group of malformations that includes hypoplastic right and left heart syndromes, extreme forms of Ebstein anomaly, and (rarely) true univentricular hearts. Incidence numbers of SCD in this group as a whole are unknown. Surgical palliation in most cases includes either partial or total cavopulmonary connections. Arrhythmias are usually of atrial origin because of right atrial scarring, dilatation, or hypertrophy. Usually, high ventricular rates are poorly tolerated.

There is also an increased risk of ventricular arrhythmias that might be attributed to the morphology, function, and myocardial quality of the systemic ventricle (e.g., dilatation and presence of advanced ventricular hypertrophy of the systemic ventricle)and associated anomalies (e.g., non-compaction cardiomyopathy of the systemic ventricle). Myocardial fibrosis, as can be detected by CMR using LGE, was associated with dilatation, hypertrophy, and dysfunction of the systemic ventricle, with a higher prevalence of nsVT compared with patients without LGE on CMR.⁴⁰

Eisenmenger Syndrome

Patients with Eisenmenger syndrome are at increased risk of SCD. In one series of 77 patients, SCD death occurred in 63% of patients, but was not related to arrhythmias.⁴¹ Nonsustained VTs were frequently present in this group, but did not result in SCD. Cardiac deaths are probably related to progressive heart failure and hypoxemia. Administration of drugs is problematic because many drugs are not tolerated and cause adverse events.

Implanted Cardioverter Defibrillator Therapy

Only small studies are available evaluating the cause of SCD in patients with ICDs; however, patients with LVOT obstruction, aortic coarctation, or univentricular heart are at higher risk of SD. The incidence of SCD remains high in postoperative patients with congenital aortic stenosis (3% after 10 years, 13% after 20 years, and 20% after 30 years). Although VA as the underlying cause of SCD is likely, only limited data are available. An ICD should be implanted after an aborted SCD and can be considered in patients with unexplained syncope without defined and reversible cause, similar to other adult structural heart disease guidelines.13,27 Complex anatomy and altered venous access (e.g., implantation of lead in an anatomic left ventricle, cavopulmonary connections) can hamper ICD implantation. Although potentially lifesaving, significant adverse effects on the quality of life have been reported in these often young patients, especially after ICD shocks.⁴² In addition, lead failure is relatively high, possibly because of a more active lifestyle in young patients.⁴³