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Late problems in tetralogy of Fallot—recognition, management, and prevention
Cardiol Clin 20 (2002) 395–404
Late problems in tetralogy of Fallot—recognition, management, and prevention Judith Therrien, MDa,*, Gerald Ross Marx, MDb, Michael A. Gatzoulis, MD, PhDc a
Toronto General Hospital, 200 Elizabeth Street, 12 EN Room 213, University of Toronto, Ontario, M5G 2C4, Canada b Children’s Hospital, 300 Longwood Avenue, Boston, Ma. 02115, USA c Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK
Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease after age one year with an incidence approaching 10% of all forms of congenital heart disease. Most children who are now repaired experience increasing longterm survival and good quality of life [1–3]. Late complications, however, may occur as they reach adulthood, and careful follow up of these patients is warranted. Anatomy The defect in TOF is due to antero-cephalad deviation of the outlet septum resulting in four features: (i) right ventricular outflow tract obstruction (RVOTO) which may be infundibular, valvar or (usually) a combination of both, with or without supravalvar or branch pulmonary artery stenosis; (ii) a nonrestrictive VSD; (iii) an overriding aorta (<50%), and (iv) consequent right ventricular hypertrophy (Fig. 1). The so-called pentalogy of Fallot also has an ASD. Accompanying features can include additional VSDs, anomalous coronary arteries, a right-sided aortic arch, aortic root dilation, aortic regurgitation, and aortopulmonary collaterals. Surgical repair Most adults will have had surgery, either palliative or, more commonly, reparative by the time
* Corresponding author. E-mail address: [email protected] (J. Therrien).
they present to the cardiologist. Rarely, an adult patient will present without previous operations. The focus of this article will be on the late outcome of adult patients after surgical repair of their tetralogy of Fallot. Reparative surgery involves closing the VSD and relieving the RVOTO (Fig. 2). The latter may involve: • Pulmonary valvotomy (as in most instances the pulmonary valve is involved, being ‘‘bicuspid’’ and dysplastic). • Resection of infundibular muscle (which represents the major site of RVOTO). • Right ventricular outflow tract (RVOT) or subannular patch (a patch across the right ventricular outflow tract RVOT that does not disrupt the integrity of the pulmonary valve annulus). RVOT patching, combined with infundibular resection, relieves the restrictive right ventricular (RV) outflow. • Transannular patch (a patch across the pulmonary valve annulus that disrupts the integrity of the pulmonary valve annulus and usually creates free pulmonary regurgitation). A transannular patch is used when the pulmonary valve annulus is restrictive. • Pulmonary valve implantation (homograft valve or porcine bioprosthesis). ‘‘Routinely’’ performed in adolescents and adults undergoing late repair, as these patients usually do not tolerate pulmonary regurgitation well, hence the need for a competent RVOT and bioprosthetic valve implantation.
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Fig. 1. Diagrammatic representation of tetralogy of Fallot. 1. Pulmonary stenosis; 2. Ventricular septal defect; 3. Overriding aorta; 4. Right ventricular hypertrophy. RA ¼ right atrium; RV ¼ right ventricle; LA ¼ left atrium; LV ¼ left ventricle; Ao ¼ aorta; PA ¼ pulmopulmonary artery. (From Mullins CE, Mayer DC: Congenital Heart Disease: A Diagrammatic Atlas. New York, Wiley-Liss, 1988; with permission.)
• An extracardiac conduit placed between the RV and pulmonary artery (in patients with pulmonary atresia, congenital or acquired, and for an anomalous coronary artery). • Angioplasty/patch augmentation of central pulmonary arteries, in patients with hypoplastic main pulmonary trunk and/or stenoses of the central pulmonary arteries. • A patent foramen ovale or secundum ASD, if present, needs closure. In the newborn or infant with marked right ventricular outflow tract obstruction and relative pulmonary artery hypoplasia, the surgeon may leave the foramen ovale patent to act as a safety feature post-operatively. Additional treatable lesions or muscular VSDs need also to be addressed at the time of initial repair. Early on, data suggested that significant residual right ventricular outflow tract obstruction was a major determinant of poor outcome. Therefore, the surgeon’s primary goal was to surgically alleviate any anatomic obstruction. Surgical approaches to the repair of tetralogy have evolved over the years. [4–8]. Hence, early cohorts underwent repair through a right ventriculotomy, [7]
Fig. 2. Diagrammatic representation of the surgical repair of tetralogy of Fallot. 1. Patch closure of ventricular septal defect; 2. Right ventricular outflow and main pulmonary artery outflow patch (transannular patch). RA ¼ right atrium; RV ¼ right ventricle; LA ¼ left atrium; LV ¼ left ventricle; Ao ¼ aorta; PA ¼ pulmopulmonary artery. (From Mullins CE, Mayer DC: Congenital Heart Disease: A Diagrammatic Atlas. New York, Wiley-Liss, 1988; with permission.)
with ‘‘complete relief ’’ of RVOT obstruction often necessitating the use of a large transannular patch, which usually creates free pulmonary regurgitation (PR). Recent data, however, has shown detrimental long-term effects of a right large ventriculotomy and chronic PR on RV function [9], with a propensity to clinical arrhythmia and sudden cardiac death (SCD) [1,10]. This has lead to a modified approach of repairing the lesion with a combined transatrial/transpulmonary approach involving closure of the VSD and relief of the RVOT obstruction through the right atrium and the pulmonary artery [5,6]. A limited RV incision is often required for patch augmentation of the RVOT and/or the pulmonary valve annulus. Routine and generous transannular patching has thus been abandoned. Every effort is now made to maintain the integrity and competence of the pulmonary valve. It is of note that residual RVOT pressure gradients present in the immediate post-operative period, previously thought to carry a poor long-term prognosis, often regress within days. Furthermore, mild to moderate residual RVOT obstruction in isolation is well tolerated longterm. Avoidance of free PR at the expense of some, albeit not severe, residual pulmonary stenosis is now a key therapeutic goal of reparative surgery.
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The timing of repair has also changed. Contemporary patients often undergo primary repair at presentation or when they become symptomatic [4,5,8]. This approach may convey long-term benefits as it abolishes the cyanosis early in life and, by normalizing pulmonary blood flow, promotes pulmonary artery growth. Most adult patients with repaired tetralogy, however, had one or more previous palliative procedures prior to undergoing later repair. Adult patients, operated many years ago, may have had one or more previous palliative procedures prior to undergoing later repair. Rarely, an adult patient may present only having undergone such a palliative operation. Such procedures include the classic Blalock-Taussig shunt (subclavian artery to right pulmonary artery connection); Waterston shunt (ascending aorta to right pulmonary artery); Potts shunt (descending aorta to left pulmonary artery); and other types of central shunts with interposed grafts. The intention of augmenting pulmonary blood flow is usually accomplished. However, complications can be significant including pulmonary artery stenosis and diminished growth, excessive pulmonary blood flow with pulmonary artery hypertension and eventually pulmonary vascular obstructive disease, and chronic left ventricular volume overload. These deleterious effects can be encountered in the adult patient with ‘‘complete’’ repairs. Shunt procedures have largely been abandoned in favor of earlier repairs. Occasionally a shunt procedure may still be performed in the very young or small (premature) infant with or without hypoplastic pulmonary arteries. Today’s shunt is most often the ‘‘modified’’ Blalock-Taussig shunt using a Goretex tube, thus better ‘‘tailoring’’ the size and therefore amount of pulmonary artery blood flow. Late problems after surgical repair The overall survival of patients who have had operative repair is excellent, provided the VSD has been closed, the RVOT obstruction has been relieved satisfactorily and severe PR, which may lead to RV dilation and RV dysfunction, is absent. A 32-to 36-year survival of 86% and 85% have been reported [2,3]. Most adults with previous repair of tetralogy of Fallot lead a good quality of life [1–3]. Over 85% of patients after intracardiac repair are asymptomatic on follow-up. Symptoms do occur in about 10 to 15% of patients at 20 years following initial repair [11,12], and may take two main forms: palpitations from atrial and
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ventricular tachycardias ; and diminished exercise tolerance, usually from progressive right ventricular dilation secondary to chronic PR. Mechanical problems Significant pulmonary regurgitation Significant (PR) is almost always encountered when the transannular patch repair technique has been employed. PR is usually well tolerated if mild to moderate. Severe chronic PR, however, may lead to symptomatic RV dysfunction [9]. The severity of PR, and its deleterious long-term effects are augmented by co-existing proximal or distal pulmonary artery stenosis, or pulmonary artery hypertension. Until recently, the severity of PR has been difficult to quantify. Investigators have employed pulsed Doppler echocardiographic interrogation of antegrade versus retrograde pulmonary blood flow to measure a regurgitant fraction [13]. MRI phased velocity mapping can produce a similar regurgitant fraction. The association of ‘‘severe PR’’, with or without distal pulmonary artery hypertension or stenosis, can result in a large volume of PR and right ventricular dilation. ‘‘Free PR’’ can also be associated with normal or only mildly increased right ventricular size, which, if echo findings support it [14], may be an example of so-called ‘‘restrictive physiology’’. Some investigators maintain that restrictive physiology inhibits the magnitude of PR, thereby resulting in less RV dilation and dysfunction. Right ventricular dilation RV dilation is usually due to residual RVOT lesions and/or (long standing free PR RVOT obstruction) [9] or as a consequence of surgical scar (transventricular approach). Significant tricuspid regurgitation (TR) may occur as a consequence of RV dilations, which begets more RV dilation. Restrictive right ventricle Restrictive RV physiology after surgical repair is thought to be due to myocardial ischemia and necrosis from inadequate myocardial protection at the time of surgery [15]. Restrictive RV physiology is usually not a major clinical problem. There is a debate as to whether restrictive RV physiology is beneficial in adults (increasing exercise capacity, preventing RV dilation) or whether it causes exercise intolerance [14,16].
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Residual right ventricular outflow tract obstruction Residual RVOT obstruction can occur at the infundibular, at the level of the pulmonary valve and main pulmonary trunk and/or distally, beyond the bifurcation and occasionally into the branches of the left and right pulmonary arteries.
A theoretical cause of left ventricular diastolic dysfunction can be a result of ventricular/ventricular interaction. The markedly dilated right ventricular, especially when hypertensive may cause significant abnormal displacement of the ventricular septum into the left ventricular cavity potentially causing alterations in left ventricular filling.
Aneurysmal dilation of the RVOT
Endocarditis
This is relatively common in patients with previous pericardial transannular patch repair and significant PR. Aneurysmal dilation of the RVOT can be associated with regional RV hypokinesis. Swirling of blood can be inferred from color flow Doppler Signals in the aneurysmal right ventricular outflow tract regions. Ostensibly this should be an area of significant energy loss. To date, no episodes of sudden rupture of these regions have been reported. Furthermore, this area can be the focus of sustained ventricular tachycardia.
Residual lesions leading to turbulent flow (residual VSD patch leak, RVOT obstruction, PR, TR) encountered in most patients after initial repair, can serve as substrate for endocarditis. Patients with turbulent flows in the RV to PA conduits may be at increased risk. Patients with palliative shunts and associated cyanosis are at significant risk of endocarditis at the region of the shunt itself.
Electrical problems Residual ventricular septal defect
Heart block
Residual ventricular septal defect (VSD) can be encountered from either partial patch dehiscence or failure of complete closure at the time of surgery or alternatively, an undetected muscular VSD. Additional muscular ventricular septal defects have been reported in up to 5 to10% of patients with Tetralogy of Fallot. These defects can be difficult to detect, even at the time of surgery, being either within the RV infundibular apex, or at the anterior muscular septum.
As a result of surgery, a right bundle branch block (RBBB) pattern is almost universal in patients who underwent repair of tetralogy of Fallot via a right ventriculotomy. Characteristically, the RBBB involves a short and narrow first part with a taller and broader second part of the QRS complex (Fig. 3). RBBB with left anterior hemiblock, so-called bifascicular block, is also common (approximately 15% of postoperative patients). Bifascicular block, when isolated, does not lead to complete heart block (unless there has been transient AV block in the immediate post-operative period) nor does it increase the risk of sudden death. Bifascicular block combined with late PR prolongation, however, occasionally heralds high-degree AV block. In other words, late onset of complete heart block is rare, even in tetralogy patients with bifascicular block.
Aortic regurgitation with or without aortic root dilation Residual aortic regurgitation is due to damage to the aortic valve during VSD closure or secondary to an intrinsic aortic root abnormality (more common in patients with pulmonary atresia and systemic to pulmonary artery collaterals). The pathological substrate for aortic root dilation seems to be cystic medial necrosis [17]. Left ventricular dysfunction Occasionally left ventricular dysfunction can be seen from a variety of factors including inadequate myocardial protection during previous repair(s), chronic LV volume overload due to long-standing palliative arterial shunts and/or residual VSD, injury to anomalous coronary artery (uncommon) or long standing cyanosis before repair.
Supraventricular arrhythmia Atrial flutter and atrial fibrillation are relatively common in the current cohort of adults with previous tetralogy repair. Atrial tachyarrhythmia occurs in about one third of adult patients and contributes to late morbidity and even mortality [18]. Atrial flutter and fibrillation are more common in patients who had long-lasting systemic-topulmonary artery shunts—and therefore persisting volume overload—and those who required early
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ular contraction (PVC) however has been debated. Correlation between the presence of PVCs and ventricular tachycardia or sudden death has been both invoked and refuted. Ventricular ectopy of grade II or greater, according to the modified Lown criteria (>30 uniform ventricular extrasystoles in any hour) appeared to be associated with increased risk of SCD but more recent studies have not shown such a relationship [1,19]. Ventricular tachycardia
Fig. 3. Electrocardiogram of tetralogy of Fallot after surgical repair. Note the wide right bundle branch block (160 msec).
reoperations for residual hemodynamic lesions, ie patients with a suboptimal result from initial reparative surgery. Older age at repair and moderate-to-severe tricuspid regurgitation were found to be additional predictors of late sustained atrial flutter and/or fibrillation in a recent multi-center study [1]. Often indicative of hemodynamic trouble (significant RV dilation and dysfunction, significant TR), the substrate is most likely a surgical scar in the atria and the trigger, atrial dilation. Atrial tachyarrhythmia usually presents with palpitations. Occasionally, however, patients can present with presyncope or syncope, and atrial flutter has been postulated as a possible cause of SCD, as these relatively young adult patients have the ability for one-to-one atrio-ventricular conduction.
Sustained monomorphic ventricular tachycardia (VT) is relatively uncommon [1]. Re-entry is the most common pathophysiologic mechanism and multiple factors have been implicated for its pathogenesis [20]. The usual arrhythmia focus is in the RVOT in the area of the previous infundibulectomy or VSD closure during tetralogy repair. In approximately 20% of cases the re-entry focus can be multiple, involving the body of the right ventricle. RV dilation [21] from impaired hemodynamics, and stretch with slowed ventricular activation [10] are also contributory to the creation of re-entry circuits within the right ventricle. The QRS duration from the standard surface ECG has been shown to correlate well with RV size in these patients [10,22]. A maximum QRS duration of 180 ms or more is a highly sensitive marker for sustained VT and SCD in adult patients with previous repair of tetralogy [10] (Fig. 4). QRS prolongation in these patients reflects: (i) initial damage to the bundle, during tetralogy repair [23] (right ventriculotomy, relief of muscular subpulmonary stenosis and suture placement for VSD patch closure); and (ii) late progressive QRS prolongation secondary to RV dilation, which in turn is almost invariably the result of chronic PR. A recent multi-center study [1] has shown that QRS change with time may be a more sensitive and specific predictor of patients at risk. New, absolute QRS predictive values for sustained ventricular tachycardia will be required for patients undergoing tetralogy repair in the current era, as most of them undergo repair via the right atrium and pulmonary artery and not through a right ventriculotomy, which was the norm until the late 1980s. Initial QRS prolongation immediately after repair is, therefore, significantly shorter in contemporary cohorts.
Premature ventricular contraction Non-sustained ventricular arrhythmia on Holter is very common (up to 60%) following repair of tetralogy. The significance of premature ventric-
Sudden cardiac death The reported incidence of sudden death, presumably arrhythmic, in late follow-up series varies
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Fig. 4. Plot of maximum QRS duration in 182 patients with repaired tetralogy of Fallot. Those with syncope due to sustained monomorphic ventricular tachycardia (9 patients, squares), atrial flutter (1 patient, asterix) and sudden cardiac death (4 patients, triangles) are plotted separately on the right column. (From Gatzoulis et al, Circulation 1995;92:231–7; with permission.)
between 0.5 to 6% over 30 years, accounting approximately for one third to one half of late deaths [2,3]. In a recent study the risk of sudden death increased incrementally after the first 20 years from repair of tetralogy (1.2 and 2.2% at 10 and 20 years respectively increased to 4% and 6% at 25 and 35 years) [1]. Older age at repair and relative postoperative RV hypertension (to LV) have been previously shown to be risk factors for late sudden death [2]. Transannular patching, predisposing to free PR, and accelerated rate of QRS prolongation were additional predictors of sudden death in our recent multi-center study [3]. Patients with sustained monomorphic ventricular tachycardia and those dying suddenly, shared a common electrophysiologic and hemodynamic substrate, suggesting a common pathogenic and pathophysiologic mechanism. Patients who died suddenly, however, had a much later repair compared to patients presenting with sustained ventricular tachycardia. This in turn suggests that
LV dysfunction, secondary to long-standing cyanosis and volume overload (from palliative arterial shunts) may also be contributory to sudden death.
Reproductive issues Pregnancy The risk of pregnancy in repaired patients depends on the patient’s hemodynamic status. The risk is low, approaching that of the general population, in patients with good underlying hemodynamics. In patients with significant residual RVOT obstruction, severe PR with or without tricuspid regurgitation and RV dysfunction, the increased volume load of pregnancy may lead to heart failure and arrhythmias [24]. Furthermore, LV dysfunction, usually due to previous volume overload, may be present. This in turn increases the likelihood of complications during pregnancy and requires independent consideration.
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Genetic counseling The risk of having a child with a congenital malformation of the heart if the mother has TOF is about 6% compared to the risk of 2% if it is the father that is affected [25]. Furthermore, approximately 15% of patients with tetralogy have a deletion of chromosome 22q11 [26]. This is tested with the fluorescence in situ hybridization (FISH) test. The incidence of 22q11 deletion is especially high in patients with right aortic arch, pulmonary atresia and aortato-pulmonary collaterals. The clinical spectrum is summarized in the so-called CATCH 22 syndrome (Cardiac defect, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia [neonatal ] and 22q11 deletion). Patients with 22q11 deletion may have a propensity to late psychiatric disorder, most commonly depression. Hyperactivity and attention deficit disorder problems have been seen in younger patients. Deletion of 22q11 is usually sporadic. Affected subjects, however, have a 50% risk of transmitting the deletion to their offspring, hence the need for family screening and genetic counseling. Management of late problems after surgical repair Mechanical problems Significant pulmonary regurgitation Relief of peripheral pulmonary artery stenosis may reduce the severity of PR [27]. Pulmonary valve implantation (with either a homograft or porcine bioprosthesis) may be necessary for severe PR or a grossly calcified pulmonary valve. It carries a low operative risk [12,28] and leads to symptomatic improvement [28,29–31]. Right ventricular dilation Alleviation of peripheral pulmonary artery stenosis may lessen the degree of (PR) and, in turn, RV dilation. Timely PVR, before RV dilation and irreversible RV dysfunction ensues is of essence [30]. Concomitant tricuspid valve annuloplasty may also be necessary when at least moderate tricuspid regurgitation is present. The restrictive right ventricle Diuretics in the postoperative period should be used if restrictive RV physiology is the cause of persistent pleural effusion [32]. Maintenance of sinus rhythm and atrio-ventricular synchrony in these patients is paramount, as significant part
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of forward pulmonary blood flow—and cardiac output—depends on right atrial systole. Residual right ventricular outflow tract obstruction Surgery may be necessary for residual significant RVOT obstruction (RVSP 2/3 systemic pressure) [33]. This may involve resection of residual infundibular stenosis or placement of a RVOT or transannular patch. A valved conduit may occasionally be necessary. Balloon dilation and stenting or surgery for branch pulmonary artery stenosis may be needed. More distal peripheral pulmonary artery stenoses are best dealt with by stenting. Occasionally, patients with proximal RV outflow tract obstruction may respond to balloon dilation valvuloplasty/angioplasty. As the surgery has progressed to avoidance of a right ventriculotomy and transannular patch, some patients have some residual obstruction as a combination of a narrowed annulus, pulmonary valve leaflet dysplasia and main pulmonary artery narrowing. Some of these patients have had an excellent response to balloon dilation valvuloplasty without incurring significant PR. Aneurysmal dilation of the RVOT Although specific indicators have not been defined, progressive marked aneurismal dilation of the RVOT may warrant surgical resection [33]. Residual ventricular septal defect Surgical correction if hemodynamically significant ventricular septal defect exist (Qp/Qs 2/1 or Qp/Qs ¼ 1.52/1 if concomitant LV dilatation or dysfunction exits) [33] or if there is a history of paradoxical emboli. Dilation of the aortic root Aortic root replacement may be considered when the ascending aorta 55 mm if recent increasing aortic root diameters have been demonstrated and/or in the presence of severe aortic regurgitation [33]. Left ventricular dysfunction There is no data on the management strategy for LV dysfunction in these patients. Extrapolation from the data on ischemic and myopathic LV dysfunction would suggest that therapy with angiotensin converting enzyme inhibitors, digoxin and diuretics may be beneficial. Additional investigations to exclude co-existing coronary artery disease may be indicated.
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Electrical problems Heart block In patients with bifascicular block combined with late PR prolongation (PR > 0.20 msec), Holter or EPS is warranted as these patients may require pacing. Pacemaker implantation is mandatory in all cases of postoperative complete heart block and in true trifascicular block, confirmed by EPS. Supraventricular arrhythmia Patients presenting with sustained atrial flutter and/or atrial fibrillation, should undergo a thorough assessment of their hemodynamics and should have target residual hemodynamic lesions corrected (eg, significant RV dilation from PR with consequent TR needing PVR and tricuspid valve annuloplasty). Radiofrequency ablation, following mapping for atrial reentry, is now yielding better results for classical atrial flutter and/or incisional re-entrant tachycardia and should be performed either percutaneously (if there is no need for concomitant surgery) or intra-operatively at the time of surgical correction of underlying hemodynamic lesions [34]. For atrial fibrillation, a biatrial maze procedure should also be considered and ideally be performed at the time of reoperation. Anti-arrhythmic medication and the new generation of atrial anti-tachycardia pacemakers can be used as adjunctive therapeutic tools. Premature ventricular contraction Sudden cardiac death following repair of tetralogy in patients with frequent PVCs is uncommon [1–3]. Currently there is no justification for prophylactic anti-arrhythmic therapy to suppress Holter ventricular arrhythmias in this relatively low risk population. Ventricular tachycardia Abnormal right-sided hemodynamics, predominantly RV dilation due to PR with or without pulmonary stenosis have been very common in patients presenting with sustained ventricular tachycardia [1,11]. A detailed hemodynamic assessment is, therefore, of paramount importance. Furthermore, interventions to repair underlying residual lesions, usually right-sided, should be an essential part of risk modification and arrhythmia management in these patients. Transcatheter (if there is no need for surgery) or concomitant intra-operative ablative procedures of
the VT pathway should be performed [34]. The role of AICD implantation in these patients is unclear. Anti-arrhythmic therapy has clearly a role for the symptomatic patient, but one cannot overemphasize the need for addressing underlying hemodynamic lesions and ablating the arrhythmia focus [1,11,34]. Sudden cardiac death Patients with resuscitated SCD should probably receive an AICD. AICD implantation is usually an adjuvant therapy for secondary prevention of sustained ventricular tachycardia and sudden cardiac death, even after repair of residual hemodynamic problems. Reproductive issues Pregnancy All patients with repaired tetralogy should have specialist cardiologic counseling before conception and evaluation early in pregnancy. Fetal echocardiography is recommended at approximately 16 to 18 weeks’ gestation. Genetic counseling Chromosome analysis is warranted due to the increased incidence of TOF in trisomy 21. The FISH test, to exclude 22qD should be considered. Prevention of late problems after surgical repair Mechanical problems Significant pulmonary regurgitation Recent changes in the surgical technique [5,6] with a less aggressive approach towards complete relief of RVOT obstruction and avoidance of a transannular patch will lessen the degree of PR. Right ventricular dilation The newer transatrial approach [5] (rather than transventricular) at the time of corrective surgery will lessen the degree of RV damage [35,36]. Changes in the surgical technique with a less aggressive approach towards complete relief of RVOT obstruction with avoidance of transannular patches [5,6] and subsequent free PR will also lessen the degree of RV dilation and dysfunction over time. The restrictive right ventricle Improved myocardial protection may reduce the degree of RV myocardial ischemia at the
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time of surgery and in turn the incidence of postoperative restrictive RV physiology. Aneurysmal dilation of RVOT Minimizing the extent of RVOT incision and the size of the prosthetic patch used for RVOT reconstruction may lessen the incidence of RVOT aneurysmal dilation. Dilation of aortic root There is no data on the effect of beta blocking therapy in these patients. Left ventricular dysfunction Proceeding with surgical correction at an early age [4,5,8], avoiding prolonged cyanosis and the need for palliative shunts and ensuring adequate myocardial protection at the time of surgery may significantly reduce the incidence of postoperative LV dysfunction. Modifying risk factors for premature coronary artery disease may also be indicated to protect against the later development of LV dysfunction. Endocarditis All patients with repaired tetralogy of Fallot require life-long protection against endocarditis [33]. Electrical problems Supraventricular arrhythmia A surgical approach that would minimize atrial scars as well as avoid significant residual hemodynamic lesions causing RA dilation may lead to a lower incidence of atrial flutter and fibrillation in these patients. Sustained ventricular tachycardia A surgical approach that would minimize ventricular scarring as well as avoid significant residual hemodynamic lesions causing RV dilation may lead to a lower incidence of ventricular tachycardia [5,35,36]. Sudden cardiac death High-risk patients for SCD (primary or secondary prevention) may benefit from AICD implantation. Summary Most adults with previous repair of tetralogy of Fallot lead unrestricted lives and are asymptomatic. Residual RVOT problems such as signifi-
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cant PR and/or RVOT obstruction however are common and often lead to gradual RV dilation and dysfunction with consequent supraventricular or ventricular arrhythmias. Hemodynamic causes for the tachyarrhythmia should be sought and corrected, and therapy directed towards suppressing the arrhythmia (antiarrhythmics, cryoablation or AICD) should be carried out as well. Recent changes in the surgical approaches to the repair of tetralogy at the time initial repair may well translate into a reduced incidence of late complications.
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[23] Norgard G, Gatzoulis M, Moraes F, et al. The relationship between type of outflow tract repair and postoperative right ventricular diastolic physiology in tetralogy of Fallot: implications for longterm outcome. Circulation 1996;94:3276–81. [24] Siu SC, Colman JM. Heart disease and pregnancy. Education in Heart. Heart 2001;85:710–15. [25] Perloff JK, Child JS. Genetics, epidemiology, counseling and prevention. In: Zorab K, editor. Congenital Heart Disease in Adults. ed 2. Philadelphia, WB Saunders, 1998, p. 165–88. [26] Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 1998;32:492–8. [27] Chaturvedi RR, Kilner P, White P, et al. Increased airway pressure and simulated branch pulmonary stenosis increase pulmonary regurgitation after repair of tetralogy of Fallot: real-time analysis using conductance catheter technique. Circulation 1997;95:643–9. [28] Yemets IM, Williams WG, Webb GD, et al. Pulmonary valve replacement late after repair of tetralogy of Fallot. Ann Thorac Surg 1997;64: 526–30. [29] Bove EL, Byrum CJ, Thomas FD, et al. The influence of pulmonary insufficiency on ventricular function following repair of tetralogy of Fallot. J Thorac Cardiovasc Surg 1983;85:691–6. [30] Therrien J, Siu S, Liu P, et al. Pulmonary valve replacement in adults late after repair of tetralogy of Fallot: Are we operating too late? J Am Coll Cardiol 2000;36:1670–5. [31] Warner KG, Anderson JE, Fulton DR, et al. Restoration of the pulmonary valve reduces right ventricular volume overload after previous repair of tetralogy of Fallot. Circulation 1993;88:II189–97. [32] Cullen S, Shore D, Redington A. Characterization of right ventricular diastolic performance after complete repair of tetralogy of Fallot: Restrictive physiology predicts slow postoperative recovery. Circulation 1995;91:1782–9. [33] Therrien J, Dore A, Gersony W, et al. Canadian Cardiovascular Society. CCS Consensus Conference 2001 update: recommendations for the management of adults with congenital heart disease. Part I. Can J Cardiol 2001;17:940–59. [34] Therrien J, Siu S, Harris L, et al. Impact of Pulmonary Valve Replacement on Arrhythmia Propensity Late after Repair of Tetralogy of Fallot. Circulation 2001;103:2489–94. [35] Dietl CA, Cazzaniga ME, Dubner SJ, et al. Lifethreatening arrhythmias and RV dysfunction after surgical repair of tetralogy of Fallot: Comparison between transventricular and transatrial approaches. Circulation 1994;90[part 2]:II7–12. [36] Kawashima Y, Matsuda H, Hirose H, et al. Ninety consecutive corrective operations for tetralogy of Fallot with or without minimal right ventriculotomy. J Thorac Cardiovasc Surg 1985;90:856–63.
Late problems in tetralogy of Fallot—recognition, management, and prevention Judith Therrien, MDa,*, Gerald Ross Marx, MDb, Michael A. Gatzoulis, MD, PhDc a
Toronto General Hospital, 200 Elizabeth Street, 12 EN Room 213, University of Toronto, Ontario, M5G 2C4, Canada b Children’s Hospital, 300 Longwood Avenue, Boston, Ma. 02115, USA c Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK
Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease after age one year with an incidence approaching 10% of all forms of congenital heart disease. Most children who are now repaired experience increasing longterm survival and good quality of life [1–3]. Late complications, however, may occur as they reach adulthood, and careful follow up of these patients is warranted. Anatomy The defect in TOF is due to antero-cephalad deviation of the outlet septum resulting in four features: (i) right ventricular outflow tract obstruction (RVOTO) which may be infundibular, valvar or (usually) a combination of both, with or without supravalvar or branch pulmonary artery stenosis; (ii) a nonrestrictive VSD; (iii) an overriding aorta (<50%), and (iv) consequent right ventricular hypertrophy (Fig. 1). The so-called pentalogy of Fallot also has an ASD. Accompanying features can include additional VSDs, anomalous coronary arteries, a right-sided aortic arch, aortic root dilation, aortic regurgitation, and aortopulmonary collaterals. Surgical repair Most adults will have had surgery, either palliative or, more commonly, reparative by the time
* Corresponding author. E-mail address: [email protected] (J. Therrien).
they present to the cardiologist. Rarely, an adult patient will present without previous operations. The focus of this article will be on the late outcome of adult patients after surgical repair of their tetralogy of Fallot. Reparative surgery involves closing the VSD and relieving the RVOTO (Fig. 2). The latter may involve: • Pulmonary valvotomy (as in most instances the pulmonary valve is involved, being ‘‘bicuspid’’ and dysplastic). • Resection of infundibular muscle (which represents the major site of RVOTO). • Right ventricular outflow tract (RVOT) or subannular patch (a patch across the right ventricular outflow tract RVOT that does not disrupt the integrity of the pulmonary valve annulus). RVOT patching, combined with infundibular resection, relieves the restrictive right ventricular (RV) outflow. • Transannular patch (a patch across the pulmonary valve annulus that disrupts the integrity of the pulmonary valve annulus and usually creates free pulmonary regurgitation). A transannular patch is used when the pulmonary valve annulus is restrictive. • Pulmonary valve implantation (homograft valve or porcine bioprosthesis). ‘‘Routinely’’ performed in adolescents and adults undergoing late repair, as these patients usually do not tolerate pulmonary regurgitation well, hence the need for a competent RVOT and bioprosthetic valve implantation.
0733-8651/02/$ - see front matter 2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 3 3 - 8 6 5 1 ( 0 2 ) 0 0 0 1 0 - 3
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Fig. 1. Diagrammatic representation of tetralogy of Fallot. 1. Pulmonary stenosis; 2. Ventricular septal defect; 3. Overriding aorta; 4. Right ventricular hypertrophy. RA ¼ right atrium; RV ¼ right ventricle; LA ¼ left atrium; LV ¼ left ventricle; Ao ¼ aorta; PA ¼ pulmopulmonary artery. (From Mullins CE, Mayer DC: Congenital Heart Disease: A Diagrammatic Atlas. New York, Wiley-Liss, 1988; with permission.)
• An extracardiac conduit placed between the RV and pulmonary artery (in patients with pulmonary atresia, congenital or acquired, and for an anomalous coronary artery). • Angioplasty/patch augmentation of central pulmonary arteries, in patients with hypoplastic main pulmonary trunk and/or stenoses of the central pulmonary arteries. • A patent foramen ovale or secundum ASD, if present, needs closure. In the newborn or infant with marked right ventricular outflow tract obstruction and relative pulmonary artery hypoplasia, the surgeon may leave the foramen ovale patent to act as a safety feature post-operatively. Additional treatable lesions or muscular VSDs need also to be addressed at the time of initial repair. Early on, data suggested that significant residual right ventricular outflow tract obstruction was a major determinant of poor outcome. Therefore, the surgeon’s primary goal was to surgically alleviate any anatomic obstruction. Surgical approaches to the repair of tetralogy have evolved over the years. [4–8]. Hence, early cohorts underwent repair through a right ventriculotomy, [7]
Fig. 2. Diagrammatic representation of the surgical repair of tetralogy of Fallot. 1. Patch closure of ventricular septal defect; 2. Right ventricular outflow and main pulmonary artery outflow patch (transannular patch). RA ¼ right atrium; RV ¼ right ventricle; LA ¼ left atrium; LV ¼ left ventricle; Ao ¼ aorta; PA ¼ pulmopulmonary artery. (From Mullins CE, Mayer DC: Congenital Heart Disease: A Diagrammatic Atlas. New York, Wiley-Liss, 1988; with permission.)
with ‘‘complete relief ’’ of RVOT obstruction often necessitating the use of a large transannular patch, which usually creates free pulmonary regurgitation (PR). Recent data, however, has shown detrimental long-term effects of a right large ventriculotomy and chronic PR on RV function [9], with a propensity to clinical arrhythmia and sudden cardiac death (SCD) [1,10]. This has lead to a modified approach of repairing the lesion with a combined transatrial/transpulmonary approach involving closure of the VSD and relief of the RVOT obstruction through the right atrium and the pulmonary artery [5,6]. A limited RV incision is often required for patch augmentation of the RVOT and/or the pulmonary valve annulus. Routine and generous transannular patching has thus been abandoned. Every effort is now made to maintain the integrity and competence of the pulmonary valve. It is of note that residual RVOT pressure gradients present in the immediate post-operative period, previously thought to carry a poor long-term prognosis, often regress within days. Furthermore, mild to moderate residual RVOT obstruction in isolation is well tolerated longterm. Avoidance of free PR at the expense of some, albeit not severe, residual pulmonary stenosis is now a key therapeutic goal of reparative surgery.
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The timing of repair has also changed. Contemporary patients often undergo primary repair at presentation or when they become symptomatic [4,5,8]. This approach may convey long-term benefits as it abolishes the cyanosis early in life and, by normalizing pulmonary blood flow, promotes pulmonary artery growth. Most adult patients with repaired tetralogy, however, had one or more previous palliative procedures prior to undergoing later repair. Adult patients, operated many years ago, may have had one or more previous palliative procedures prior to undergoing later repair. Rarely, an adult patient may present only having undergone such a palliative operation. Such procedures include the classic Blalock-Taussig shunt (subclavian artery to right pulmonary artery connection); Waterston shunt (ascending aorta to right pulmonary artery); Potts shunt (descending aorta to left pulmonary artery); and other types of central shunts with interposed grafts. The intention of augmenting pulmonary blood flow is usually accomplished. However, complications can be significant including pulmonary artery stenosis and diminished growth, excessive pulmonary blood flow with pulmonary artery hypertension and eventually pulmonary vascular obstructive disease, and chronic left ventricular volume overload. These deleterious effects can be encountered in the adult patient with ‘‘complete’’ repairs. Shunt procedures have largely been abandoned in favor of earlier repairs. Occasionally a shunt procedure may still be performed in the very young or small (premature) infant with or without hypoplastic pulmonary arteries. Today’s shunt is most often the ‘‘modified’’ Blalock-Taussig shunt using a Goretex tube, thus better ‘‘tailoring’’ the size and therefore amount of pulmonary artery blood flow. Late problems after surgical repair The overall survival of patients who have had operative repair is excellent, provided the VSD has been closed, the RVOT obstruction has been relieved satisfactorily and severe PR, which may lead to RV dilation and RV dysfunction, is absent. A 32-to 36-year survival of 86% and 85% have been reported [2,3]. Most adults with previous repair of tetralogy of Fallot lead a good quality of life [1–3]. Over 85% of patients after intracardiac repair are asymptomatic on follow-up. Symptoms do occur in about 10 to 15% of patients at 20 years following initial repair [11,12], and may take two main forms: palpitations from atrial and
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ventricular tachycardias ; and diminished exercise tolerance, usually from progressive right ventricular dilation secondary to chronic PR. Mechanical problems Significant pulmonary regurgitation Significant (PR) is almost always encountered when the transannular patch repair technique has been employed. PR is usually well tolerated if mild to moderate. Severe chronic PR, however, may lead to symptomatic RV dysfunction [9]. The severity of PR, and its deleterious long-term effects are augmented by co-existing proximal or distal pulmonary artery stenosis, or pulmonary artery hypertension. Until recently, the severity of PR has been difficult to quantify. Investigators have employed pulsed Doppler echocardiographic interrogation of antegrade versus retrograde pulmonary blood flow to measure a regurgitant fraction [13]. MRI phased velocity mapping can produce a similar regurgitant fraction. The association of ‘‘severe PR’’, with or without distal pulmonary artery hypertension or stenosis, can result in a large volume of PR and right ventricular dilation. ‘‘Free PR’’ can also be associated with normal or only mildly increased right ventricular size, which, if echo findings support it [14], may be an example of so-called ‘‘restrictive physiology’’. Some investigators maintain that restrictive physiology inhibits the magnitude of PR, thereby resulting in less RV dilation and dysfunction. Right ventricular dilation RV dilation is usually due to residual RVOT lesions and/or (long standing free PR RVOT obstruction) [9] or as a consequence of surgical scar (transventricular approach). Significant tricuspid regurgitation (TR) may occur as a consequence of RV dilations, which begets more RV dilation. Restrictive right ventricle Restrictive RV physiology after surgical repair is thought to be due to myocardial ischemia and necrosis from inadequate myocardial protection at the time of surgery [15]. Restrictive RV physiology is usually not a major clinical problem. There is a debate as to whether restrictive RV physiology is beneficial in adults (increasing exercise capacity, preventing RV dilation) or whether it causes exercise intolerance [14,16].
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Residual right ventricular outflow tract obstruction Residual RVOT obstruction can occur at the infundibular, at the level of the pulmonary valve and main pulmonary trunk and/or distally, beyond the bifurcation and occasionally into the branches of the left and right pulmonary arteries.
A theoretical cause of left ventricular diastolic dysfunction can be a result of ventricular/ventricular interaction. The markedly dilated right ventricular, especially when hypertensive may cause significant abnormal displacement of the ventricular septum into the left ventricular cavity potentially causing alterations in left ventricular filling.
Aneurysmal dilation of the RVOT
Endocarditis
This is relatively common in patients with previous pericardial transannular patch repair and significant PR. Aneurysmal dilation of the RVOT can be associated with regional RV hypokinesis. Swirling of blood can be inferred from color flow Doppler Signals in the aneurysmal right ventricular outflow tract regions. Ostensibly this should be an area of significant energy loss. To date, no episodes of sudden rupture of these regions have been reported. Furthermore, this area can be the focus of sustained ventricular tachycardia.
Residual lesions leading to turbulent flow (residual VSD patch leak, RVOT obstruction, PR, TR) encountered in most patients after initial repair, can serve as substrate for endocarditis. Patients with turbulent flows in the RV to PA conduits may be at increased risk. Patients with palliative shunts and associated cyanosis are at significant risk of endocarditis at the region of the shunt itself.
Electrical problems Residual ventricular septal defect
Heart block
Residual ventricular septal defect (VSD) can be encountered from either partial patch dehiscence or failure of complete closure at the time of surgery or alternatively, an undetected muscular VSD. Additional muscular ventricular septal defects have been reported in up to 5 to10% of patients with Tetralogy of Fallot. These defects can be difficult to detect, even at the time of surgery, being either within the RV infundibular apex, or at the anterior muscular septum.
As a result of surgery, a right bundle branch block (RBBB) pattern is almost universal in patients who underwent repair of tetralogy of Fallot via a right ventriculotomy. Characteristically, the RBBB involves a short and narrow first part with a taller and broader second part of the QRS complex (Fig. 3). RBBB with left anterior hemiblock, so-called bifascicular block, is also common (approximately 15% of postoperative patients). Bifascicular block, when isolated, does not lead to complete heart block (unless there has been transient AV block in the immediate post-operative period) nor does it increase the risk of sudden death. Bifascicular block combined with late PR prolongation, however, occasionally heralds high-degree AV block. In other words, late onset of complete heart block is rare, even in tetralogy patients with bifascicular block.
Aortic regurgitation with or without aortic root dilation Residual aortic regurgitation is due to damage to the aortic valve during VSD closure or secondary to an intrinsic aortic root abnormality (more common in patients with pulmonary atresia and systemic to pulmonary artery collaterals). The pathological substrate for aortic root dilation seems to be cystic medial necrosis [17]. Left ventricular dysfunction Occasionally left ventricular dysfunction can be seen from a variety of factors including inadequate myocardial protection during previous repair(s), chronic LV volume overload due to long-standing palliative arterial shunts and/or residual VSD, injury to anomalous coronary artery (uncommon) or long standing cyanosis before repair.
Supraventricular arrhythmia Atrial flutter and atrial fibrillation are relatively common in the current cohort of adults with previous tetralogy repair. Atrial tachyarrhythmia occurs in about one third of adult patients and contributes to late morbidity and even mortality [18]. Atrial flutter and fibrillation are more common in patients who had long-lasting systemic-topulmonary artery shunts—and therefore persisting volume overload—and those who required early
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ular contraction (PVC) however has been debated. Correlation between the presence of PVCs and ventricular tachycardia or sudden death has been both invoked and refuted. Ventricular ectopy of grade II or greater, according to the modified Lown criteria (>30 uniform ventricular extrasystoles in any hour) appeared to be associated with increased risk of SCD but more recent studies have not shown such a relationship [1,19]. Ventricular tachycardia
Fig. 3. Electrocardiogram of tetralogy of Fallot after surgical repair. Note the wide right bundle branch block (160 msec).
reoperations for residual hemodynamic lesions, ie patients with a suboptimal result from initial reparative surgery. Older age at repair and moderate-to-severe tricuspid regurgitation were found to be additional predictors of late sustained atrial flutter and/or fibrillation in a recent multi-center study [1]. Often indicative of hemodynamic trouble (significant RV dilation and dysfunction, significant TR), the substrate is most likely a surgical scar in the atria and the trigger, atrial dilation. Atrial tachyarrhythmia usually presents with palpitations. Occasionally, however, patients can present with presyncope or syncope, and atrial flutter has been postulated as a possible cause of SCD, as these relatively young adult patients have the ability for one-to-one atrio-ventricular conduction.
Sustained monomorphic ventricular tachycardia (VT) is relatively uncommon [1]. Re-entry is the most common pathophysiologic mechanism and multiple factors have been implicated for its pathogenesis [20]. The usual arrhythmia focus is in the RVOT in the area of the previous infundibulectomy or VSD closure during tetralogy repair. In approximately 20% of cases the re-entry focus can be multiple, involving the body of the right ventricle. RV dilation [21] from impaired hemodynamics, and stretch with slowed ventricular activation [10] are also contributory to the creation of re-entry circuits within the right ventricle. The QRS duration from the standard surface ECG has been shown to correlate well with RV size in these patients [10,22]. A maximum QRS duration of 180 ms or more is a highly sensitive marker for sustained VT and SCD in adult patients with previous repair of tetralogy [10] (Fig. 4). QRS prolongation in these patients reflects: (i) initial damage to the bundle, during tetralogy repair [23] (right ventriculotomy, relief of muscular subpulmonary stenosis and suture placement for VSD patch closure); and (ii) late progressive QRS prolongation secondary to RV dilation, which in turn is almost invariably the result of chronic PR. A recent multi-center study [1] has shown that QRS change with time may be a more sensitive and specific predictor of patients at risk. New, absolute QRS predictive values for sustained ventricular tachycardia will be required for patients undergoing tetralogy repair in the current era, as most of them undergo repair via the right atrium and pulmonary artery and not through a right ventriculotomy, which was the norm until the late 1980s. Initial QRS prolongation immediately after repair is, therefore, significantly shorter in contemporary cohorts.
Premature ventricular contraction Non-sustained ventricular arrhythmia on Holter is very common (up to 60%) following repair of tetralogy. The significance of premature ventric-
Sudden cardiac death The reported incidence of sudden death, presumably arrhythmic, in late follow-up series varies
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Fig. 4. Plot of maximum QRS duration in 182 patients with repaired tetralogy of Fallot. Those with syncope due to sustained monomorphic ventricular tachycardia (9 patients, squares), atrial flutter (1 patient, asterix) and sudden cardiac death (4 patients, triangles) are plotted separately on the right column. (From Gatzoulis et al, Circulation 1995;92:231–7; with permission.)
between 0.5 to 6% over 30 years, accounting approximately for one third to one half of late deaths [2,3]. In a recent study the risk of sudden death increased incrementally after the first 20 years from repair of tetralogy (1.2 and 2.2% at 10 and 20 years respectively increased to 4% and 6% at 25 and 35 years) [1]. Older age at repair and relative postoperative RV hypertension (to LV) have been previously shown to be risk factors for late sudden death [2]. Transannular patching, predisposing to free PR, and accelerated rate of QRS prolongation were additional predictors of sudden death in our recent multi-center study [3]. Patients with sustained monomorphic ventricular tachycardia and those dying suddenly, shared a common electrophysiologic and hemodynamic substrate, suggesting a common pathogenic and pathophysiologic mechanism. Patients who died suddenly, however, had a much later repair compared to patients presenting with sustained ventricular tachycardia. This in turn suggests that
LV dysfunction, secondary to long-standing cyanosis and volume overload (from palliative arterial shunts) may also be contributory to sudden death.
Reproductive issues Pregnancy The risk of pregnancy in repaired patients depends on the patient’s hemodynamic status. The risk is low, approaching that of the general population, in patients with good underlying hemodynamics. In patients with significant residual RVOT obstruction, severe PR with or without tricuspid regurgitation and RV dysfunction, the increased volume load of pregnancy may lead to heart failure and arrhythmias [24]. Furthermore, LV dysfunction, usually due to previous volume overload, may be present. This in turn increases the likelihood of complications during pregnancy and requires independent consideration.
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Genetic counseling The risk of having a child with a congenital malformation of the heart if the mother has TOF is about 6% compared to the risk of 2% if it is the father that is affected [25]. Furthermore, approximately 15% of patients with tetralogy have a deletion of chromosome 22q11 [26]. This is tested with the fluorescence in situ hybridization (FISH) test. The incidence of 22q11 deletion is especially high in patients with right aortic arch, pulmonary atresia and aortato-pulmonary collaterals. The clinical spectrum is summarized in the so-called CATCH 22 syndrome (Cardiac defect, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia [neonatal ] and 22q11 deletion). Patients with 22q11 deletion may have a propensity to late psychiatric disorder, most commonly depression. Hyperactivity and attention deficit disorder problems have been seen in younger patients. Deletion of 22q11 is usually sporadic. Affected subjects, however, have a 50% risk of transmitting the deletion to their offspring, hence the need for family screening and genetic counseling. Management of late problems after surgical repair Mechanical problems Significant pulmonary regurgitation Relief of peripheral pulmonary artery stenosis may reduce the severity of PR [27]. Pulmonary valve implantation (with either a homograft or porcine bioprosthesis) may be necessary for severe PR or a grossly calcified pulmonary valve. It carries a low operative risk [12,28] and leads to symptomatic improvement [28,29–31]. Right ventricular dilation Alleviation of peripheral pulmonary artery stenosis may lessen the degree of (PR) and, in turn, RV dilation. Timely PVR, before RV dilation and irreversible RV dysfunction ensues is of essence [30]. Concomitant tricuspid valve annuloplasty may also be necessary when at least moderate tricuspid regurgitation is present. The restrictive right ventricle Diuretics in the postoperative period should be used if restrictive RV physiology is the cause of persistent pleural effusion [32]. Maintenance of sinus rhythm and atrio-ventricular synchrony in these patients is paramount, as significant part
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of forward pulmonary blood flow—and cardiac output—depends on right atrial systole. Residual right ventricular outflow tract obstruction Surgery may be necessary for residual significant RVOT obstruction (RVSP 2/3 systemic pressure) [33]. This may involve resection of residual infundibular stenosis or placement of a RVOT or transannular patch. A valved conduit may occasionally be necessary. Balloon dilation and stenting or surgery for branch pulmonary artery stenosis may be needed. More distal peripheral pulmonary artery stenoses are best dealt with by stenting. Occasionally, patients with proximal RV outflow tract obstruction may respond to balloon dilation valvuloplasty/angioplasty. As the surgery has progressed to avoidance of a right ventriculotomy and transannular patch, some patients have some residual obstruction as a combination of a narrowed annulus, pulmonary valve leaflet dysplasia and main pulmonary artery narrowing. Some of these patients have had an excellent response to balloon dilation valvuloplasty without incurring significant PR. Aneurysmal dilation of the RVOT Although specific indicators have not been defined, progressive marked aneurismal dilation of the RVOT may warrant surgical resection [33]. Residual ventricular septal defect Surgical correction if hemodynamically significant ventricular septal defect exist (Qp/Qs 2/1 or Qp/Qs ¼ 1.52/1 if concomitant LV dilatation or dysfunction exits) [33] or if there is a history of paradoxical emboli. Dilation of the aortic root Aortic root replacement may be considered when the ascending aorta 55 mm if recent increasing aortic root diameters have been demonstrated and/or in the presence of severe aortic regurgitation [33]. Left ventricular dysfunction There is no data on the management strategy for LV dysfunction in these patients. Extrapolation from the data on ischemic and myopathic LV dysfunction would suggest that therapy with angiotensin converting enzyme inhibitors, digoxin and diuretics may be beneficial. Additional investigations to exclude co-existing coronary artery disease may be indicated.
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Electrical problems Heart block In patients with bifascicular block combined with late PR prolongation (PR > 0.20 msec), Holter or EPS is warranted as these patients may require pacing. Pacemaker implantation is mandatory in all cases of postoperative complete heart block and in true trifascicular block, confirmed by EPS. Supraventricular arrhythmia Patients presenting with sustained atrial flutter and/or atrial fibrillation, should undergo a thorough assessment of their hemodynamics and should have target residual hemodynamic lesions corrected (eg, significant RV dilation from PR with consequent TR needing PVR and tricuspid valve annuloplasty). Radiofrequency ablation, following mapping for atrial reentry, is now yielding better results for classical atrial flutter and/or incisional re-entrant tachycardia and should be performed either percutaneously (if there is no need for concomitant surgery) or intra-operatively at the time of surgical correction of underlying hemodynamic lesions [34]. For atrial fibrillation, a biatrial maze procedure should also be considered and ideally be performed at the time of reoperation. Anti-arrhythmic medication and the new generation of atrial anti-tachycardia pacemakers can be used as adjunctive therapeutic tools. Premature ventricular contraction Sudden cardiac death following repair of tetralogy in patients with frequent PVCs is uncommon [1–3]. Currently there is no justification for prophylactic anti-arrhythmic therapy to suppress Holter ventricular arrhythmias in this relatively low risk population. Ventricular tachycardia Abnormal right-sided hemodynamics, predominantly RV dilation due to PR with or without pulmonary stenosis have been very common in patients presenting with sustained ventricular tachycardia [1,11]. A detailed hemodynamic assessment is, therefore, of paramount importance. Furthermore, interventions to repair underlying residual lesions, usually right-sided, should be an essential part of risk modification and arrhythmia management in these patients. Transcatheter (if there is no need for surgery) or concomitant intra-operative ablative procedures of
the VT pathway should be performed [34]. The role of AICD implantation in these patients is unclear. Anti-arrhythmic therapy has clearly a role for the symptomatic patient, but one cannot overemphasize the need for addressing underlying hemodynamic lesions and ablating the arrhythmia focus [1,11,34]. Sudden cardiac death Patients with resuscitated SCD should probably receive an AICD. AICD implantation is usually an adjuvant therapy for secondary prevention of sustained ventricular tachycardia and sudden cardiac death, even after repair of residual hemodynamic problems. Reproductive issues Pregnancy All patients with repaired tetralogy should have specialist cardiologic counseling before conception and evaluation early in pregnancy. Fetal echocardiography is recommended at approximately 16 to 18 weeks’ gestation. Genetic counseling Chromosome analysis is warranted due to the increased incidence of TOF in trisomy 21. The FISH test, to exclude 22qD should be considered. Prevention of late problems after surgical repair Mechanical problems Significant pulmonary regurgitation Recent changes in the surgical technique [5,6] with a less aggressive approach towards complete relief of RVOT obstruction and avoidance of a transannular patch will lessen the degree of PR. Right ventricular dilation The newer transatrial approach [5] (rather than transventricular) at the time of corrective surgery will lessen the degree of RV damage [35,36]. Changes in the surgical technique with a less aggressive approach towards complete relief of RVOT obstruction with avoidance of transannular patches [5,6] and subsequent free PR will also lessen the degree of RV dilation and dysfunction over time. The restrictive right ventricle Improved myocardial protection may reduce the degree of RV myocardial ischemia at the
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time of surgery and in turn the incidence of postoperative restrictive RV physiology. Aneurysmal dilation of RVOT Minimizing the extent of RVOT incision and the size of the prosthetic patch used for RVOT reconstruction may lessen the incidence of RVOT aneurysmal dilation. Dilation of aortic root There is no data on the effect of beta blocking therapy in these patients. Left ventricular dysfunction Proceeding with surgical correction at an early age [4,5,8], avoiding prolonged cyanosis and the need for palliative shunts and ensuring adequate myocardial protection at the time of surgery may significantly reduce the incidence of postoperative LV dysfunction. Modifying risk factors for premature coronary artery disease may also be indicated to protect against the later development of LV dysfunction. Endocarditis All patients with repaired tetralogy of Fallot require life-long protection against endocarditis [33]. Electrical problems Supraventricular arrhythmia A surgical approach that would minimize atrial scars as well as avoid significant residual hemodynamic lesions causing RA dilation may lead to a lower incidence of atrial flutter and fibrillation in these patients. Sustained ventricular tachycardia A surgical approach that would minimize ventricular scarring as well as avoid significant residual hemodynamic lesions causing RV dilation may lead to a lower incidence of ventricular tachycardia [5,35,36]. Sudden cardiac death High-risk patients for SCD (primary or secondary prevention) may benefit from AICD implantation. Summary Most adults with previous repair of tetralogy of Fallot lead unrestricted lives and are asymptomatic. Residual RVOT problems such as signifi-
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cant PR and/or RVOT obstruction however are common and often lead to gradual RV dilation and dysfunction with consequent supraventricular or ventricular arrhythmias. Hemodynamic causes for the tachyarrhythmia should be sought and corrected, and therapy directed towards suppressing the arrhythmia (antiarrhythmics, cryoablation or AICD) should be carried out as well. Recent changes in the surgical approaches to the repair of tetralogy at the time initial repair may well translate into a reduced incidence of late complications.
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