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EP challenges in adult congenital heart disease
CONTEMPORARY REVIEW
EP challenges in adult congenital heart disease Paul Khairy, MD, PhD From the Adult Congenital Heart Center and Electrophysiology Service, Montreal Heart Institute, University of Montreal, Canada. Congenital heart disease is the most prevalent type of inborn defect, with a rapidly growing and aging patient population that is increasing in complexity. Indicative of the remarkable progress in pediatric cardiac care, adults now outnumber children with congenital heart disease. Adults with congenital heart disease constitute a distinct and heterogeneous population of patients with unique needs, concerns, and challenges. Arrhythmias figure foremost among the issues encountered and are the leading cause of morbidity, hospital admissions, and mortality. Several novel and singular challenges of unparalleled diversity are encountered in the arrhythmia management of adults with congenital heart disease and span the entire spectrum of bradyarrhythmias and tachyarrhythmias. The nascent
field of adult congenital electrophysiology requires an integration of standard electrophysiology proficiencies with a thorough appreciation for congenital heart disease anatomy, physiology, and surgical interventions. The objective of this review is to highlight commonly confronted arrhythmia issues and themes, discuss particular challenges, review recent relevant literature, and summarize current management trends.
Heart malformations, the most common type of inborn defects, afflict an estimated 75 of 1,000 live births,1 with diverse underlying pathologies. Over the past half century, the field of congenital heart disease has been marked by astonishing progress, particularly in surgical, perioperative, and interventional care, permitting survival into adulthood in the vast majority.2 Tellingly, the number of adults now exceeds children with congenital heart disease, as the population of patients continues to expand, age, and increase in complexity.3 After a protracted or relatively uneventful childhood course, the adult patient with congenital heart disease typically has experienced a long adolescent period with neither hemodynamic nor arrhythmia concerns. In adulthood, the burden of disease is substantial, with arrhythmias figuring prominently. Arrhythmias are the leading cause of morbidity and hospital admissions.4 – 6 Sudden death of presumed arrhythmic etiology is the most common cause of demise. Fortunately, the overall incidence is relatively low. Nevertheless, sudden deaths often transpire in the third or fourth decades of life, with an up to 100-fold increased risk compared to healthy age-matched controls.7,8 The entire spectrum of bradyarrhythmias and tachyarrhythmias is encountered in adults with congenital heart disease.5,9 Arrhythmia onset may herald a changing hemo-
dynamic profile or reflect a chronic potentially complex interplay among anatomic features, preexisting or ongoing mechanical and/or hypoxic stress, postoperative sequelae, residual defects, and comorbidities.10 Electrophysiology challenges in adults with congenital heart disease are considerable and often unique. Although many are lesion specific, the objective of this review is to provide a synopsis of commonly confronted arrhythmia issues, discuss their particularities, and review relevant current management trends.
This work was supported in part by the Canada Research Chair in Electrophysiology and Adult Congenital Heart Disease to Dr. Khairy. Address reprint requests and correspondence: Dr. Paul Khairy, Adult Congenital Heart Center, Montreal Heart Institute, 5000 Belanger Street East, Montreal, QC, Canada, H1T 1C8. E-mail address: [email protected].
KEYWORDS Adult congenital heart disease; Electrophysiology; Pacemaker; Defibrillator; Ablation; Cardiac resynchronization therapy (Heart Rhythm 2008;5:1464 –1472) © 2008 Heart Rhythm Society. All rights reserved.
Bradyarrhythmias and pacemakers Bradyarrhythmias requiring pacemakers are highly prevalent in adults with congenital heart disease, with an incidence that varies according to the type of defect and surgical correction. Sinus node dysfunction, atrioventricular (AV) or intraatrial conduction block, and His-Purkinje disease are common. Sinus node dysfunction occasionally is present at birth (e.g., heterotaxy syndrome with left atrial isomerism, left-juxtaposed atrial appendages) but more frequently occurs after cardiac surgery (e.g., intraatrial baffle repair for transposition of the great arteries, Fontan procedures for single ventricles, superior vena cava to pulmonary artery (Glenn) connections).5,6,11 For example, in patients with Mustard baffles for transposition of the great arteries, symptomatic sinus node dysfunction is observed in 64% and 82% at 5 and 16 years of follow-up, respectively.12 Displacement of the AV conduction system confers susceptibility to impaired AV nodal conduction, as exemplified by the estimated 2% annual incidence of spontaneous AV block in congenitally corrected transposition of the great
1547-5271/$ -see front matter © 2008 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2008.05.026
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arteries.13 Surgeries commonly associated with acquired AV block include closure of AV canal or ventricular septal defects, atrial reduction procedures, and valve interventions. When permanent pacing is indicated, challenges include lack of or obstructed venous access, difficulties in lead positioning, high rates of lead complications, and coexisting intracardiac shunts.
Venous access Anomalies of the superior veins are found in 9% of patients with congenital heart disease.14 A persistent left superior vena cava is most prevalent in heterotaxy syndromes, conotruncal anomalies (e.g., tetralogy of Fallot), and left ventricular outflow tract ostructions.14 Moreover, in adults with congenital heart disease, venous occlusion may be encountered in the setting of prior transvenous leads. In a cohort of 85 young patients with transvenous leads, 25% experienced complete or partial obstruction (i.e., ⬎70% with collateral flow) at 6.5 years following implantation.15 Age, size, growth, and lead factors did not appear to predict such occlusions. Additional impediments to transvenous lead access include obstructed baffles or conduits. Baffle obstruction in transposition of the great arteries typically occurs at the superior limb of the systemic venous pathway and has been reported in 36%.12 Systemic venous pathway obstruction is 3.5 times more likely to occur in Mustard compared to Senning baflles.12 In addition to compromising transvenous lead access, severe obstruction may produce the superior vena cava syndrome. Routine venography prior to pacemaker implantation may be revealing (Figure 1). Recanalization of occluded superior baffle limbs has been performed by percutaneous angioplasty, radiofrequency perforation wires, and balloon expandable stents to permit lead implantation.16
Lead positioning Lead placement may be further complicated by synthetic patches, baffles, conduits, absence of usual structures such as atrial appendages, and extensive fibrosis.17 In transposi-
Figure 1 Contrast venography prior to pacemaker implantation in a patient with sinus node dysfunction, transposition of the great arteries, and Mustard baffle. A: Left arm phlebography revealed patent left subclavian and innominate veins, with a large dilated tortuous thoracic vein draining into the inferior vena cava. B: Angiography via subclavian venous access exposed complete obstruction of the superior vena cava. Percutaneous recanalization was required to permit transvenous lead access.
1465 tion of the great arteries with Mustard or Senning baffles, the atrial lead is placed in the systemic venous atrium, usually in the retained portion of left atrium or proximal left atrial appendage (Figure 2). Avoidance of phrenic nerve stimulation merits particular attention, especially in the distal left atrial appendage. When inserting a lead into a left subpulmonary ventricle, care is required to ensure that a baffle leak is not traversed to enter the right subaortic ventricle. In univentricular hearts with Fontan palliation, systemic venous return is diverted to the pulmonary artery, usually precluding direct transvenous access to the ventricle.18 Despite extensive areas of low voltage, acceptable atrial pacing thresholds and adequate P-wave sensing may be attained in the majority of adults with Fontan surgery.19 With classic modified right atrium to pulmonary connections, transvenous atrial pacing is generally feasible, and ventricular pacing via the coronary sinus may be achieved in selected cases.20 In patients with more modern total cavopulmonary connections, some surgical variants of intracardiac lateral tunnels may likewise permit transvenous access to the coronary sinus.
Lead dysfunction Patients with congenital heart disease and pacemakers or implantable cardioverter-defibrillators (ICDs) face a lifelong prospect of potential device and lead-related complications. Multiple reinterventions often are required. In 497 young patients with pacemakers, congenital heart disease was an independent risk factor for lead failure.21 However, 77% of patients were younger than 18 years at time of implantation, and 52% of leads were epicardial, including more than 40% of leads in 117 patients 18 years or older. In a series of 122 patients with epicardial pacemakers, reintervention for lead fracture or dysfunction was required in 36% over a mean follow-up of 6.4 years.22 Comparisons between transvenous and epicardial lead approaches are confounded by the common practice of implanting epicardial devices in conjunction with other forms of heart surgery. Nevertheless, epicardial leads are generally associated with higher atrial
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Figure 2 Atrial lead placement in transposition of the great arteries with Mustard baffle. Contrast angiography is performed in the superior vena cava (SVC) in a patient with transposition of the great arteries, Mustard baffle, sinus node dysfunction, and a transvenous atrial pacemaker. Note partial obstruction at the SVC–superior baffle limb junction. The tip of the permanent transvenous atrial lead is in the midportion of the left atrial appendage (LAA) (arrow). Phrenic nerve capture did not occur at this site. The distal tip of a decapolar catheter is deep within the LAA. At this site (asterisk), diaphragmatic stimulation occurred at a low pacing threshold. MV ⫽ mitral valve.
and ventricular lead thresholds and reduced generator longevity although somewhat mitigated by steroid-eluting systems.23 Similar rates of reintervention are noted,23–25 as fracture and exit block occur more frequently with epicardial systems, whereas transvenous leads are at higher risk for insulation breaks and dislodgments.21
Lead extraction Given the high incidence of lead failure and growing patient population, lead extraction procedures are increasingly required in adults with congenital heart disease. Particular challenges are encountered in this patient population. In a cohort of 175 adults with attempted laser extraction of 270 leads, those with congenital heart disease were younger at implantation and had older leads at extraction, more rightsided implants, a higher proportion of active fixation leads, and particular anatomic features.26 The latter included intracardiac shunting and targeted leads in subpulmonary left ventricles, left atrial appendages, severely dilated and/or dysfunctional subpulmonary right ventricles, and partially obstructed baffles.26 Despite these complexities, success rates (91%) and complication rates (6%) were similar to those in patients without congenital heart disease. However, a longer procedural time was required.26
Intracardiac shunts In adults with congenital heart disease, atrial or ventricular intracardiac shunts may occur in isolation, as components of
Heart Rhythm, Vol 5, No 10, October 2008 more complex structural disease, in surgically palliated hearts with residual or iatrogenic defects, via baffle leaks, or by deliberately created interchamber communications.12,23 In the presence of intracardiac shunting, transvenous leads are associated with increased risk for presumably paradoxical systemic thromboemboli. This risk was quantified in a multicenter study of 202 patients with intracardiac shunts followed for 12 years.23 Annualized rates of systemic thromboemboli were 2% vs 0.5% with transvenous and epicardial leads, respectively. In multivariate analyses, presence of transvenous leads independently predicted risk for systemic thromboemboli (hazard ratio 2.6). In patients with transvenous leads, older age, presence of atrial fibrillation or flutter, and ongoing phlebotomies were associated with increased risk for systemic thromboemboli. Importantly, this multicenter study could not identify a lower-risk subgroup based on level of shunting (i.e., atrial, ventricular, or both), presence or absence of confirmed right-to-left flow, oxygen saturation, ventricular function, lead chamber, or number of leads.23 Although the study was underpowered to assess protective effects of medical therapy, no favorable trends were elicited. Nine of 14 events occurred despite warfarin therapy, with international normalized ratios ⱖ2.5 in three patients, ⬍2.0 in four, and unknown in two. Despite unresolved issues, our center currently recommends shunt closure prior to transvenous lead implantation, if possible (Figure 3). When not feasible, an epicardial approach is considered. In the presence of trivial residual shunting, anticoagulation is empirically pursued.
Risk stratification for sudden death Predicting future sudden arrhythmic deaths is a challenging task, particularly in primary prevention. Even in ischemic or dilated cardiomyopathy with several randomized primary prevention ICD trials of more than 8,000 patients, risk stratification remains a topic of debate. More accurate and sophisticated screening methods are continuously sought. The current state of knowledge in adults with congenital heart disease is bleaker in comparison, with no prospective randomized study. At present, the most common forms of congenital heart disease in ICD recipients are tetralogy of Fallot,27 transposition of the great arteries with intraatrial baffles,28 and aortic stenosis, consistent with the seemingly highest-risk lesions.7,29 The greatest progress in risk stratification has been for patients with tetralogy of Fallot. In tetralogy of Fallot, the overall incidence of sudden death is approximately 0.15% per year,7 which if considered linear amounts to less than 2% per decade. Within this relatively low-risk population, observational studies have identified risk factors for ventricular tachycardia and sudden death, including QRS duration ⱖ180 ms,30 older age at repair, transannular right ventricular outflow tract patch, frequent ventricular ectopy,31 left ventricular systolic dysfunction,32 and inducible sustained ventricular tachycardia.33 Stratification by electrophysiologic studies appears most helpful in patients deemed at moderate risk by a combination of static and
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Figure 3 Closure of intracardiac shunts prior to pacemaker implantation. A patient with complex transposition of the great arteries and a Mustard baffle required dual-chamber pacing for symptomatic high-grade AV block. A: Angiography in the superior vena cava (SVC) revealed a baffle leak at the superior limb (arrows). B: Contrast injection in the inferior vena cava (IVC) revealed a larger shunt at the inferior limb of the Mustard baffle. C: Baffle leaks were closed by two Amplatz devices and covered stents prior to transvenous lead placement (left atrial appendage, left subpulmonary ventricle), shown in the anteroposterior view.
dynamic noninvasive risk factors.34 Risk stratification schemes continue to be refined as the knowledge base expands. Known noninvasive and invasive risk factors should complement sound clinical judgment.35
Implantable cardioverter-defibrillators In adults with congenital heart disease who survive a cardiac arrest, have a reasonable life expectancy, and no identifiable potentially reversible trigger, ICD indications are rarely disputed. Similarly, in patients with sustained ventricular tachycardia, ICDs are increasingly used for secondary prevention therapy either as a first-line measure or if uncertainty remains after attempted catheter ablation or directed hemodynamic and/or arrhythmic surgery. Standard primary prevention indications (i.e., systemic left ventricular ejection fraction ⱕ30% despite optimal therapy) are present in the minority of adults with congenital heart disease who receive prophylactic ICDs.
1467 At present, the largest ICD study on congenital heart disease is a multicenter cohort of 121 patients with tetralogy of Fallot enrolled from 11 sites, with a median follow-up of 4 years.27 Patients with primary and secondary prevention indications experienced high rates of appropriate shocks (7.7% and 9.8% per year, respectively). A risk score for appropriate shocks in primary prevention was derived from surgical, hemodynamic, electrocardiographic, and electrophysiologic factors. One point was attributed to QRS duration ⱖ180 ms; two points each for prior palliative shunt, inducible sustained ventricular tachycardia, ventriculotomy incision, and nonsustained ventricular tachycardia; and three points for left ventricular end-diastolic pressure ⱖ12 mmHg. No appropriate shocks occurred in patients with ⬍3 points (“low risk”). In patients with 3–5 points (“intermediate risk”) and ⬎5 points (“high risk”), appropriate shocks were received by 3.8% and 17.5% per year, respectively.27 Importantly, this risk score was derived in selected patients in whom ICDs were deemed indicated a priori and remains to be validated in an independent dataset. To date, ICD studies in congenital heart disease have relied on appropriate shocks as a primary endpoint, which is an imperfect surrogate marker for sudden death. Moreover, high rates of inappropriate shocks have consistently been reported. In patients with tetralogy of Fallot, inappropriate shocks occurred in 5.8% per year.27 Additionally, 5% experienced acute complications and 21% late lead-related complications. Therefore, challenges with risk stratification must be considered within the context of these complications.29,36 ICDs should be programmed with care, bearing in mind the potential psychological burden. For example, in tetralogy of Fallot, monomorphic ventricular tachycardia may be amenable to antitachycardia overdrive pacing. Programming higher defibrillation detection thresholds and/or prolonging time to detection may further prevent unnecessary shocks. Technical challenges to ICD lead implantation may be unique. When vascular access limitations preclude transvenous leads or when thromboembolic risks are prohibitive, epicardial systems may be required. These approaches require some creativity and an understanding of anatomy and defibrillation vectors. Epicardial patches have largely been abandoned due to complications such as pericardial restriction. In a multicenter series that assembled 22 predominantly pediatric patients with ICDs devoid of transvenous shocking coils or epicardial patches, configurations included subcutaneous arrays and epicardially or subcutaneously placed transvenous ICD leads.37 High defibrillation thresholds were noted in 18%, and 32% required system revision over a follow-up of 2 years.37 More recently, a computer-based assessment tool was developed with imagebased finite element modeling to compare electric fields and projected defibrillation thresholds with different configurations.38 A variety of extracardiac orientations were predicted by changing anatomic relations and varying electrode lengths. Among the important observations, can placement
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Figure 4 Transvenous cardiac resynchronization therapy in congenital heart disease. A transvenous biventricular ICD system was implanted in a patient with congenitally corrected transposition of the greater arteries and dextrocardia. Right (A) and left (B) anterior oblique views are depicted. The ICD lead was placed in the subpulmonary left ventricle (LV). A lead was inserted in the coronary sinus to pace the subaortic right ventricle (RV). RA ⫽ right atrium.
opposite rather than ipsilateral to a subcutaneous electrode resulted in lower defibrillation thresholds.38 Such an interactive image-based approach may prove helpful in guiding individualized lead placement when standard approaches are contraindicated.
Cardiac resynchronization therapy In adults with congenital heart disease, major challenges in cardiac resynchronization therapy include patient selection, technical issues related to lead placement, unique forms of dyssynchrony, and means of assessing outcomes. Traditional indications are derived from multiple randomized clinical trials and consist of systemic left ventricular systolic dysfunction, a wide QRS interval, and New York Heart Association (NYHA) class 3 or 4 symptoms despite optimal medical therapy. In contrast, supportive evidence for cardiac resynchronization therapy in congenital heart disease is limited to case series and small crossover studies in the acute postoperative setting.39,40 Notably, NYHA functional classification should be interpreted with caution in adults with congenital heart dis-
Figure 5 Hybrid approach to cardiac resynchronization therapy in congenital heart disease. A transvenous ICD lead was positioned in the subpulmonary left ventricle in a patient with congenitally corrected transposition of the great arteries, prosthetic right-sided AV valve, and permanent slow atrial fibrillation. Partial atresia of the coronary sinus ostium precluded transvenous lead placement for cardiac resynchronization therapy. Via a minithoracotomy incision, an epicardial lead was sutured to the lateral free wall of the subaortic right ventricle (arrows). Anteroposterior (A) and lateral (B) chest x-ray views are displayed.
ease. Despite an alleged paucity of symptoms that reflects adaptation to a lifelong disorder, exercise capacity is generally depressed in a manner comparable to chronic heart failure.41 The heterogeneity of the patient population and singular anatomies encountered further obscure the selection of appropriate candidates. Whereas standard indications rely on QRS duration as a marker of dyssynchrony, most case series in congenital heart disease incorporate some echocardiographic metric. No uniform approach has yet emerged. Pending prospective validation, imaging studies such as tissue Doppler, strain, strain rate, three-dimensional echocardiography, and/or tissue tracking may prove valuable in guiding the selection of potential responders. In spite of these challenges, studies have begun addressing various potential substrates for cardiac resynchronization therapy in congenital heart disease. These include the more prevalent right as opposed to left bundle branch block pattern, dysfunction of a subpulmonary right ventricle, systemic right ventricular dysfunction in patients with transposition of the great arteries, multisite pacing for dyssyn-
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chrony of the univentricular heart, and acute postoperative ventricular failure. A few case series have reported favorable long-term outcomes, although analyses are subject to nonblinded assessment, confounding by concomitant surgical interventions, and lack of control groups to adjust for spontaneous improvement or response to medical therapy.39,40,42 Notwithstanding these limitations, provocative observational data suggest a low rate of nonresponders and major successes in delisting patients with advanced forms of heart failure from transplant programs, particularly in the youngest subgroups.40 Implantation strategies remain empiric. In the absence of contraindications, transvenous lead systems are generally preferred when the anatomy is favorable, including coronary sinus drainage into an accessible systemic venous atrium. Lead positioning may be particularly challenging (Figure 4). In certain circumstances, such as complete transposition of the great arteries with intraatrial baffle redirection or congenitally corrected transposition with a malformed or underdeveloped coronary sinus, a hybrid approach may be required (Figure 5). Atrial and subpulmonary ventricular leads may be inserted transvenously, with a minithoracotomy to place an epicardial systemic ventricular lead. If associated with an ICD, the defibrillator lead remains intracardiac with such an approach, which is gener-
Figure 6 Catheter ablation of an arrhythmia substrate partially covered by prosthetic material. Electrophysiologic study and catheter ablation were performed in a patient with Ebstein’s anomaly, one and a half ventricular repair (bidirectional Glenn shunt), and prosthetic tricuspid valve. A: Angiography of the right atrium in the anteroposterior view. Note the tricuspid valve prosthesis and absent right atrium to superior vena cava connection. B: Electroanatomic map in a left lateral view. Local activation times are color coded, with the wavefront spreading from white to red, orange, yellow, green, light blue, dark blue, and purple. A counterclockwise circuit revolving around the prosthetic tricuspid valve is appreciated. The site of successful irrigated radiofrequency catheter ablation that produced bidirectional isthmus block is shown in right (C) and left (D) anterior oblique view. Arrows indicate the catheter position along the inferior portion of the tricuspid valve prosthesis.
1469 ally associated with lower defibrillation thresholds.38 Finally, an entirely epicardial system may be implanted, with care to position leads remote from one another, in areas of late electromechanical activation.39,40
Catheter ablation In contrast to the limited albeit occasionally effective role of medical therapy, advances in three-dimensional mapping techniques and catheter technologies have provided new optimism for arrhythmia management in adults with congenital heart disease. With a thorough understanding and appreciation for underlying structural disease, surgical barriers, tenuous physiology, and variations in conduction system anatomy, most arrhythmias can be safely and successfully ablated.43 Careful preprocedural planning may include a detailed review of operative notes and all documented arrhythmias, visualization of three-dimensional anatomy by cardiac magnetic resonance imaging or computed tomographic scan, and ensuring qualified anesthesiology assistance, availability of “air filters” for intravenous lines, and accessibility to an intensive care unit bed postintervention. A typical procedure consists of importing cardiac magnetic resonance or computed tomographic images into a three-dimensional mapping system, performing angiography of the desired chamber, hemodynamic assessment if
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Figure 7 Electroanatomic mapping in a right atrium to pulmonary artery Fontan. An electroanatomic map (left) and imported cardiac magnetic resonance image (right) are shown in a patient with a classic modified Fontan and recalcitrant atrial tachyarrhythmias. Gray regions denote areas of dense scar. Local activation times are color coded, from white to red, orange, yellow, green, light blue, dark blue, and purple. Note the narrow channel of tissue between two dense scars. The arrhythmia circuit propagated counterclockwise around the upper scar and was successfully interrupted by ablating this narrow isthmus. CSO ⫽ coronary sinus ostium; IVC ⫽ inferior vena cava.
indicated, baseline electrophysiologic testing, induction of a clinically relevant arrhythmia if not spontaneously present, three-dimensional mapping of local activation times and barriers to conduction, use of standard techniques such as entrainment mapping to confirm the diagnosis and desired target site, actual ablation, and demonstration of lesion effectiveness. Particular challenges are numerous, not least of which is the operator resilience required for lengthy procedures. Vascular access may be compromised by prior venous cutdowns and/or multiple interventions during childhood. When venous access is limited, esophageal leads may be considered to record atrial electrograms. The chamber of interest may be formidably large, as in right atrium to pulmonary artery Fontan connections, with difficulties ensuring optimal catheter contact and transmural lesions. Baffle or conduit obstructions and acute angles may impede access to areas of interest. A stable reference catheter position may be problematic, especially when the coronary sinus is not accessible. We commonly use screw-in leads when such a situation arises. Punctures across conduits or surgical patches may be required, as for transposition of the great arteries with intraatrial baffles, univentricular hearts with total cavopulmonary connections, and surgically repaired atrial septal defects. Occasionally, arrhythmia substrates are concealed beneath patches or prosthetic material (Figure 6). Although desired tissue penetration may not be feasible, in our experience, the greatest success is achieved with irrigated radiofrequency ablation guided by precise mapping.44 Other challenges include localization of relevant anatomic structures, such as the right AV groove in Ebstein’s anomaly, avoidance of inadvertent damage to displaced conduction systems,45 and deciphering complex or multiple arrhythmia circuits. Recurrences and/or onset of new ar-
rhythmias postablation appear highest in patients with Fontan palliation for univentricular hearts.46 Single circuits may be present, with potential for long-term arrhythmia-free survival (Figure 7). By and large, quality of life is substantially improved following catheter ablation.46
Current controversies There are several ongoing controversies in arrhythmia management patterns for adults with congenital heart disease. To highlight but a few, opinions diverge as to whether transvenous or epicardial atrial leads should be favored in Fontan patients. Thrombus formation on pacing leads is an important concern given the multiple clotting factor abnormalities, increased platelet reactivity, and sluggish circulation. In the absence of a subpulmonary ventricular pump to overcome increases in afterload engendered by pulmonary emboli, hemodynamic consequences may be devastating. Indeed, in adults with univentricular hearts, thromboembolism in the Fontan pathway/pulmonary circulation is a leading cause of death.47 Whereas some recommend avoidance of transvenous leads in this context, proponents generally support long-term antiplatelet or anticoagulation therapy. Another area of controversy involves the interaction of arrhythmias in determining timing of pulmonary valve replacement in tetralogy of Fallot and the impact of surgery on modifying risk for sudden death. In patients with ventricular arrhythmias and severe pulmonary regurgitation, pulmonary valve replacement may result in hemodynamic and symptomatic improvement. However, most caregivers agree that pulmonary valve replacement alone does not fully address the underlying arrhythmic substrate. Whether directed or empiric concomitant surgical ablation provides sufficient protection against sudden death remains uncertain.48,49 In one series of patients with repaired tetralogy of Fallot, ventricular tachycardia recurred in 10% despite sur-
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gical ablation.50 Similar concerns about recurrent ventricular tachycardia and risk for sudden death are central to the debate regarding transcatheter ablation as primary therapy for sustained ventricular tachycardia in tetralogy of Fallot, in the absence of an ICD.51 Another contentious issue in the arrhythmia management of adults with congenital heart disease is the role of catheter ablation vs Fontan conversion to a total cavopulmonary connection with adjuvant surgical ablation (i.e., modified right atrial maze with or without a Cox maze III) in patients with right atrium to pulmonary artery anastomoses.47,52 Perspectives differ as to whether surgery should be considered primary therapy for atrial arrhythmias in the absence of underlying hemodynamic lesions, such as Fontan obstruction.53 Proponents of a primary surgical approach call attention to the markedly dilated and hypertrophied right atrium with reservations about transmurality and contiguity of linear catheter ablation lesions, high recurrence rates postablation, low perioperative mortality (1%), infrequent late deaths (5%), and an 86% freedom from atrial reentrant tachyarrhythmias at 5 years.54 In patients without other indications for Fontan conversion, supporters of transcatheter ablation for atrial arrhythmias emphasize its less invasive nature, very low associated morbidity and mortality, potential for long-term arrhythmia-free survival in some, reduction of arrhythmia burden with improved quality of life in most, ease of repeat intervention if required, and the fact that catheter ablation does not preclude later surgical intervention for refractory arrhythmias.18,43,46 Moreover, higher perioperative mortality rates (5%–10%) are cited,47,55,56 as is the lack of controlled studies demonstrating a net benefit of a widely applied first-line surgical approach. These ongoing controversies underscore recommendations to concentrate the care of adults with congenital heart disease within regional centers supported by collaborative multidisciplinary teams dedicated to improving outcomes, education, and research.53,57 Electrophysiology personnel with specific skills and knowledge in congenital heart disease should be integrated in such teams and provide the full range of ablative and device therapies, in addition to consultative and diagnostic services appropriate to the special needs of patients with adult congenital heart disease.57
Conclusion Dedicated clinics, research, guidelines, and associations now are acknowledging that adults with congenital heart disease compose a distinct population of patients with unique needs and concerns. Arrhythmias in adults with congenital heart disease constitute a burgeoning branch of electrophysiology, with an arguably unprecedented degree of diversity. The skill set required to maximize patient safety and optimize procedural outcomes involves merging electrophysiology proficiencies with a thorough understanding of congenital heart disease anatomy and physiology. This special area of interest is increasingly recognized in a formalized context. Arrhythmia management guidelines
1471 have begun incorporating issues relevant to this patient population, and targeted training programs are offered. At our institution, an adult congenital arrhythmia clinic was inaugurated in 2004. Although electrophysiology challenges in adults with congenital heart disease are substantial, so too is the potential to impact on quality of life and long-term survival.
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tional endocardial pacing leads in children. J Thorac Cardiovasc Surg 1999; 117:523–528. Khairy P, Roux JF, Dubuc M, et al. Laser lead extraction in adult congenital heart disease. J Cardiovasc Electrophysiol 2007;18:507–511. Khairy P, Harris L, Landzberg MJ, et al. Implantable cardioverter-defibrillators in tetralogy of Fallot. Circulation 2008;117:363–370. Khairy P, Harris L, Landzberg MJ, et al. Defibrillators in transposition of the great arteries with Mustard or Senning baffles. Heart Rhythm 2007;4:S95– S96. Yap SC, Roos-Hesselink JW, Hoendermis ES, et al. Outcome of implantable cardioverter defibrillators in adults with congenital heart disease: a multi-centre study. Eur Heart J 2007;28:1854 –1861. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet 2000;356:975–981. Harrison DA, Harris L, Siu SC, et al. Sustained ventricular tachycardia in adult patients late after repair of tetralogy of Fallot. J Am Coll Cardiol 1997;30:1368 – 1373. Ghai A, Silversides C, Harris L, et al. Left ventricular dysfunction is a risk factor for sudden cardiac death in adults late after repair of tetralogy of Fallot. J Am Coll Cardiol 2002;40:1675–1680. Khairy P, Landzberg MJ, Gatzoulis MA, et al. Value of programmed ventricular stimulation after tetralogy of Fallot repair: a multicenter study. Circulation 2004;109:1994 –2000. Khairy P. Programmed ventricular stimulation for risk stratification in patients with tetralogy of Fallot: a Bayesian perspective. Nat Clin Pract Cardiovasc Med 2007;4:292–293. Walsh EP. Practical aspects of implantable defibrillator therapy in patients with congenital heart disease. Pacing Clin Electrophysiol 2008;31:S38 – 40. Alexander ME, Cecchin F, Walsh EP, et al. Implications of implantable cardioverter defibrillator therapy in congenital heart disease and pediatrics. J Cardiovasc Electrophysiol 2004;15:72–76. Stephenson EA, Batra AS, Knilans TK, et al. A multicenter experience with novel implantable cardioverter defibrillator configurations in the pediatric and congenital heart disease population. J Cardiovasc Electrophysiol 2006;17:41– 46. Jolley M, Stinstra J, Pieper S, et al. A computer modeling tool for comparing novel ICD electrode orientations in children and adults. Heart Rhythm 2008;5: 565–572. Khairy P, Fournier A, Thibault B, et al. Cardiac resynchronization therapy in congenital heart disease. Int J Cardiol 2006;109:160 –168. Janousek J, Gebauer RA. Cardiac resynchronization therapy in pediatric and congenital heart disease. Pacing Clin Electrophysiol 2008;31:S21–23. Diller GP, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation 2005;112:828 – 835. Dubin AM, Janousek J, Rhee E, et al. Resynchronization therapy in pediatric and
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congenital heart disease patients: an international multicenter study. J Am Coll Cardiol 2005;46:2277–2283. Triedman JK, DeLucca JM, Alexander ME, et al. Prospective trial of electroanatomically guided, irrigated catheter ablation of atrial tachycardia in patients with congenital heart disease. Heart Rhythm 2005;2:700 –705. Khairy P, Fournier A, Mercier LA, et al. Wolff-Parkinson-White syndrome in d-transposition of the great arteries and mustard baffle. Heart Rhythm 2006;3: 853– 856. Khairy P, Mercier LA, Dore A, et al. Partial atrioventricular canal defect with inverted atrioventricular nodal input into an inferiorly displaced atrioventricular node. Heart Rhythm 2007;4:355–358. Triedman JK, Alexander ME, Love BA, et al. Influence of patient factors and ablative technologies on outcomes of radiofrequency ablation of intra-atrial re-entrant tachycardia in patients with congenital heart disease. J Am Coll Cardiol 2002;39:1827–1835. Khairy P, Fernandes SM, Mayer JE Jr, et al. Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation 2008; 117:85–92. Therrien J, Siu SC, Harris L, et al. Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot. Circulation 2001; 103:2489 –2494. Oosterhof T, Vliegen HW, Meijboom FJ, et al. Long-term effect of pulmonary valve replacement on QRS duration in patients with corrected tetralogy of Fallot. Heart 2007;93:506 –509. Karamlou T, Silber I, Lao R, et al. Outcomes after late reoperation in patients with repaired tetralogy of Fallot: the impact of arrhythmia and arrhythmia surgery. Ann Thorac Surg 2006;81:1786 –1793. Zeppenfeld K, Schalij MJ, Bartelings MM, et al. Catheter ablation of ventricular tachycardia after repair of congenital heart disease: electroanatomic identification of the critical right ventricular isthmus. Circulation 2007;116:2241–2252. Mavroudis C, Backer CL, Deal BJ, et al. Total cavopulmonary conversion and maze procedure for patients with failure of the Fontan operation. J Thorac Cardiovasc Surg 2001;122:863– 871. Therrien J, Dore A, Gersony W, et al. CCS Consensus Conference 2001 update: recommendations for the management of adults with congenital heart disease. Part I. Can J Cardiol 2001;17:940 –959. Backer CL, Tsao S, Deal BJ, et al. Maze procedure in single ventricle patients. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2008:44 – 48. Weinstein S, Cua C, Chan D, et al. Outcome of symptomatic patients undergoing extracardiac Fontan conversion and cryoablation. J Thorac Cardiovasc Surg 2003;126:529 –536. Agnoletti G, Borghi A, Vignati G, et al. Fontan conversion to total cavopulmonary connection and arrhythmia ablation: clinical and functional results. Heart. 2003;89(2):193–198. Landzberg MJ, Murphy DJ Jr, Davidson WR Jr, et al. Task force 4: organization of delivery systems for adults with congenital heart disease. J Am Coll Cardiol 2001;37:1187–1193.
EP challenges in adult congenital heart disease Paul Khairy, MD, PhD From the Adult Congenital Heart Center and Electrophysiology Service, Montreal Heart Institute, University of Montreal, Canada. Congenital heart disease is the most prevalent type of inborn defect, with a rapidly growing and aging patient population that is increasing in complexity. Indicative of the remarkable progress in pediatric cardiac care, adults now outnumber children with congenital heart disease. Adults with congenital heart disease constitute a distinct and heterogeneous population of patients with unique needs, concerns, and challenges. Arrhythmias figure foremost among the issues encountered and are the leading cause of morbidity, hospital admissions, and mortality. Several novel and singular challenges of unparalleled diversity are encountered in the arrhythmia management of adults with congenital heart disease and span the entire spectrum of bradyarrhythmias and tachyarrhythmias. The nascent
field of adult congenital electrophysiology requires an integration of standard electrophysiology proficiencies with a thorough appreciation for congenital heart disease anatomy, physiology, and surgical interventions. The objective of this review is to highlight commonly confronted arrhythmia issues and themes, discuss particular challenges, review recent relevant literature, and summarize current management trends.
Heart malformations, the most common type of inborn defects, afflict an estimated 75 of 1,000 live births,1 with diverse underlying pathologies. Over the past half century, the field of congenital heart disease has been marked by astonishing progress, particularly in surgical, perioperative, and interventional care, permitting survival into adulthood in the vast majority.2 Tellingly, the number of adults now exceeds children with congenital heart disease, as the population of patients continues to expand, age, and increase in complexity.3 After a protracted or relatively uneventful childhood course, the adult patient with congenital heart disease typically has experienced a long adolescent period with neither hemodynamic nor arrhythmia concerns. In adulthood, the burden of disease is substantial, with arrhythmias figuring prominently. Arrhythmias are the leading cause of morbidity and hospital admissions.4 – 6 Sudden death of presumed arrhythmic etiology is the most common cause of demise. Fortunately, the overall incidence is relatively low. Nevertheless, sudden deaths often transpire in the third or fourth decades of life, with an up to 100-fold increased risk compared to healthy age-matched controls.7,8 The entire spectrum of bradyarrhythmias and tachyarrhythmias is encountered in adults with congenital heart disease.5,9 Arrhythmia onset may herald a changing hemo-
dynamic profile or reflect a chronic potentially complex interplay among anatomic features, preexisting or ongoing mechanical and/or hypoxic stress, postoperative sequelae, residual defects, and comorbidities.10 Electrophysiology challenges in adults with congenital heart disease are considerable and often unique. Although many are lesion specific, the objective of this review is to provide a synopsis of commonly confronted arrhythmia issues, discuss their particularities, and review relevant current management trends.
This work was supported in part by the Canada Research Chair in Electrophysiology and Adult Congenital Heart Disease to Dr. Khairy. Address reprint requests and correspondence: Dr. Paul Khairy, Adult Congenital Heart Center, Montreal Heart Institute, 5000 Belanger Street East, Montreal, QC, Canada, H1T 1C8. E-mail address: [email protected].
KEYWORDS Adult congenital heart disease; Electrophysiology; Pacemaker; Defibrillator; Ablation; Cardiac resynchronization therapy (Heart Rhythm 2008;5:1464 –1472) © 2008 Heart Rhythm Society. All rights reserved.
Bradyarrhythmias and pacemakers Bradyarrhythmias requiring pacemakers are highly prevalent in adults with congenital heart disease, with an incidence that varies according to the type of defect and surgical correction. Sinus node dysfunction, atrioventricular (AV) or intraatrial conduction block, and His-Purkinje disease are common. Sinus node dysfunction occasionally is present at birth (e.g., heterotaxy syndrome with left atrial isomerism, left-juxtaposed atrial appendages) but more frequently occurs after cardiac surgery (e.g., intraatrial baffle repair for transposition of the great arteries, Fontan procedures for single ventricles, superior vena cava to pulmonary artery (Glenn) connections).5,6,11 For example, in patients with Mustard baffles for transposition of the great arteries, symptomatic sinus node dysfunction is observed in 64% and 82% at 5 and 16 years of follow-up, respectively.12 Displacement of the AV conduction system confers susceptibility to impaired AV nodal conduction, as exemplified by the estimated 2% annual incidence of spontaneous AV block in congenitally corrected transposition of the great
1547-5271/$ -see front matter © 2008 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2008.05.026
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arteries.13 Surgeries commonly associated with acquired AV block include closure of AV canal or ventricular septal defects, atrial reduction procedures, and valve interventions. When permanent pacing is indicated, challenges include lack of or obstructed venous access, difficulties in lead positioning, high rates of lead complications, and coexisting intracardiac shunts.
Venous access Anomalies of the superior veins are found in 9% of patients with congenital heart disease.14 A persistent left superior vena cava is most prevalent in heterotaxy syndromes, conotruncal anomalies (e.g., tetralogy of Fallot), and left ventricular outflow tract ostructions.14 Moreover, in adults with congenital heart disease, venous occlusion may be encountered in the setting of prior transvenous leads. In a cohort of 85 young patients with transvenous leads, 25% experienced complete or partial obstruction (i.e., ⬎70% with collateral flow) at 6.5 years following implantation.15 Age, size, growth, and lead factors did not appear to predict such occlusions. Additional impediments to transvenous lead access include obstructed baffles or conduits. Baffle obstruction in transposition of the great arteries typically occurs at the superior limb of the systemic venous pathway and has been reported in 36%.12 Systemic venous pathway obstruction is 3.5 times more likely to occur in Mustard compared to Senning baflles.12 In addition to compromising transvenous lead access, severe obstruction may produce the superior vena cava syndrome. Routine venography prior to pacemaker implantation may be revealing (Figure 1). Recanalization of occluded superior baffle limbs has been performed by percutaneous angioplasty, radiofrequency perforation wires, and balloon expandable stents to permit lead implantation.16
Lead positioning Lead placement may be further complicated by synthetic patches, baffles, conduits, absence of usual structures such as atrial appendages, and extensive fibrosis.17 In transposi-
Figure 1 Contrast venography prior to pacemaker implantation in a patient with sinus node dysfunction, transposition of the great arteries, and Mustard baffle. A: Left arm phlebography revealed patent left subclavian and innominate veins, with a large dilated tortuous thoracic vein draining into the inferior vena cava. B: Angiography via subclavian venous access exposed complete obstruction of the superior vena cava. Percutaneous recanalization was required to permit transvenous lead access.
1465 tion of the great arteries with Mustard or Senning baffles, the atrial lead is placed in the systemic venous atrium, usually in the retained portion of left atrium or proximal left atrial appendage (Figure 2). Avoidance of phrenic nerve stimulation merits particular attention, especially in the distal left atrial appendage. When inserting a lead into a left subpulmonary ventricle, care is required to ensure that a baffle leak is not traversed to enter the right subaortic ventricle. In univentricular hearts with Fontan palliation, systemic venous return is diverted to the pulmonary artery, usually precluding direct transvenous access to the ventricle.18 Despite extensive areas of low voltage, acceptable atrial pacing thresholds and adequate P-wave sensing may be attained in the majority of adults with Fontan surgery.19 With classic modified right atrium to pulmonary connections, transvenous atrial pacing is generally feasible, and ventricular pacing via the coronary sinus may be achieved in selected cases.20 In patients with more modern total cavopulmonary connections, some surgical variants of intracardiac lateral tunnels may likewise permit transvenous access to the coronary sinus.
Lead dysfunction Patients with congenital heart disease and pacemakers or implantable cardioverter-defibrillators (ICDs) face a lifelong prospect of potential device and lead-related complications. Multiple reinterventions often are required. In 497 young patients with pacemakers, congenital heart disease was an independent risk factor for lead failure.21 However, 77% of patients were younger than 18 years at time of implantation, and 52% of leads were epicardial, including more than 40% of leads in 117 patients 18 years or older. In a series of 122 patients with epicardial pacemakers, reintervention for lead fracture or dysfunction was required in 36% over a mean follow-up of 6.4 years.22 Comparisons between transvenous and epicardial lead approaches are confounded by the common practice of implanting epicardial devices in conjunction with other forms of heart surgery. Nevertheless, epicardial leads are generally associated with higher atrial
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Figure 2 Atrial lead placement in transposition of the great arteries with Mustard baffle. Contrast angiography is performed in the superior vena cava (SVC) in a patient with transposition of the great arteries, Mustard baffle, sinus node dysfunction, and a transvenous atrial pacemaker. Note partial obstruction at the SVC–superior baffle limb junction. The tip of the permanent transvenous atrial lead is in the midportion of the left atrial appendage (LAA) (arrow). Phrenic nerve capture did not occur at this site. The distal tip of a decapolar catheter is deep within the LAA. At this site (asterisk), diaphragmatic stimulation occurred at a low pacing threshold. MV ⫽ mitral valve.
and ventricular lead thresholds and reduced generator longevity although somewhat mitigated by steroid-eluting systems.23 Similar rates of reintervention are noted,23–25 as fracture and exit block occur more frequently with epicardial systems, whereas transvenous leads are at higher risk for insulation breaks and dislodgments.21
Lead extraction Given the high incidence of lead failure and growing patient population, lead extraction procedures are increasingly required in adults with congenital heart disease. Particular challenges are encountered in this patient population. In a cohort of 175 adults with attempted laser extraction of 270 leads, those with congenital heart disease were younger at implantation and had older leads at extraction, more rightsided implants, a higher proportion of active fixation leads, and particular anatomic features.26 The latter included intracardiac shunting and targeted leads in subpulmonary left ventricles, left atrial appendages, severely dilated and/or dysfunctional subpulmonary right ventricles, and partially obstructed baffles.26 Despite these complexities, success rates (91%) and complication rates (6%) were similar to those in patients without congenital heart disease. However, a longer procedural time was required.26
Intracardiac shunts In adults with congenital heart disease, atrial or ventricular intracardiac shunts may occur in isolation, as components of
Heart Rhythm, Vol 5, No 10, October 2008 more complex structural disease, in surgically palliated hearts with residual or iatrogenic defects, via baffle leaks, or by deliberately created interchamber communications.12,23 In the presence of intracardiac shunting, transvenous leads are associated with increased risk for presumably paradoxical systemic thromboemboli. This risk was quantified in a multicenter study of 202 patients with intracardiac shunts followed for 12 years.23 Annualized rates of systemic thromboemboli were 2% vs 0.5% with transvenous and epicardial leads, respectively. In multivariate analyses, presence of transvenous leads independently predicted risk for systemic thromboemboli (hazard ratio 2.6). In patients with transvenous leads, older age, presence of atrial fibrillation or flutter, and ongoing phlebotomies were associated with increased risk for systemic thromboemboli. Importantly, this multicenter study could not identify a lower-risk subgroup based on level of shunting (i.e., atrial, ventricular, or both), presence or absence of confirmed right-to-left flow, oxygen saturation, ventricular function, lead chamber, or number of leads.23 Although the study was underpowered to assess protective effects of medical therapy, no favorable trends were elicited. Nine of 14 events occurred despite warfarin therapy, with international normalized ratios ⱖ2.5 in three patients, ⬍2.0 in four, and unknown in two. Despite unresolved issues, our center currently recommends shunt closure prior to transvenous lead implantation, if possible (Figure 3). When not feasible, an epicardial approach is considered. In the presence of trivial residual shunting, anticoagulation is empirically pursued.
Risk stratification for sudden death Predicting future sudden arrhythmic deaths is a challenging task, particularly in primary prevention. Even in ischemic or dilated cardiomyopathy with several randomized primary prevention ICD trials of more than 8,000 patients, risk stratification remains a topic of debate. More accurate and sophisticated screening methods are continuously sought. The current state of knowledge in adults with congenital heart disease is bleaker in comparison, with no prospective randomized study. At present, the most common forms of congenital heart disease in ICD recipients are tetralogy of Fallot,27 transposition of the great arteries with intraatrial baffles,28 and aortic stenosis, consistent with the seemingly highest-risk lesions.7,29 The greatest progress in risk stratification has been for patients with tetralogy of Fallot. In tetralogy of Fallot, the overall incidence of sudden death is approximately 0.15% per year,7 which if considered linear amounts to less than 2% per decade. Within this relatively low-risk population, observational studies have identified risk factors for ventricular tachycardia and sudden death, including QRS duration ⱖ180 ms,30 older age at repair, transannular right ventricular outflow tract patch, frequent ventricular ectopy,31 left ventricular systolic dysfunction,32 and inducible sustained ventricular tachycardia.33 Stratification by electrophysiologic studies appears most helpful in patients deemed at moderate risk by a combination of static and
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Figure 3 Closure of intracardiac shunts prior to pacemaker implantation. A patient with complex transposition of the great arteries and a Mustard baffle required dual-chamber pacing for symptomatic high-grade AV block. A: Angiography in the superior vena cava (SVC) revealed a baffle leak at the superior limb (arrows). B: Contrast injection in the inferior vena cava (IVC) revealed a larger shunt at the inferior limb of the Mustard baffle. C: Baffle leaks were closed by two Amplatz devices and covered stents prior to transvenous lead placement (left atrial appendage, left subpulmonary ventricle), shown in the anteroposterior view.
dynamic noninvasive risk factors.34 Risk stratification schemes continue to be refined as the knowledge base expands. Known noninvasive and invasive risk factors should complement sound clinical judgment.35
Implantable cardioverter-defibrillators In adults with congenital heart disease who survive a cardiac arrest, have a reasonable life expectancy, and no identifiable potentially reversible trigger, ICD indications are rarely disputed. Similarly, in patients with sustained ventricular tachycardia, ICDs are increasingly used for secondary prevention therapy either as a first-line measure or if uncertainty remains after attempted catheter ablation or directed hemodynamic and/or arrhythmic surgery. Standard primary prevention indications (i.e., systemic left ventricular ejection fraction ⱕ30% despite optimal therapy) are present in the minority of adults with congenital heart disease who receive prophylactic ICDs.
1467 At present, the largest ICD study on congenital heart disease is a multicenter cohort of 121 patients with tetralogy of Fallot enrolled from 11 sites, with a median follow-up of 4 years.27 Patients with primary and secondary prevention indications experienced high rates of appropriate shocks (7.7% and 9.8% per year, respectively). A risk score for appropriate shocks in primary prevention was derived from surgical, hemodynamic, electrocardiographic, and electrophysiologic factors. One point was attributed to QRS duration ⱖ180 ms; two points each for prior palliative shunt, inducible sustained ventricular tachycardia, ventriculotomy incision, and nonsustained ventricular tachycardia; and three points for left ventricular end-diastolic pressure ⱖ12 mmHg. No appropriate shocks occurred in patients with ⬍3 points (“low risk”). In patients with 3–5 points (“intermediate risk”) and ⬎5 points (“high risk”), appropriate shocks were received by 3.8% and 17.5% per year, respectively.27 Importantly, this risk score was derived in selected patients in whom ICDs were deemed indicated a priori and remains to be validated in an independent dataset. To date, ICD studies in congenital heart disease have relied on appropriate shocks as a primary endpoint, which is an imperfect surrogate marker for sudden death. Moreover, high rates of inappropriate shocks have consistently been reported. In patients with tetralogy of Fallot, inappropriate shocks occurred in 5.8% per year.27 Additionally, 5% experienced acute complications and 21% late lead-related complications. Therefore, challenges with risk stratification must be considered within the context of these complications.29,36 ICDs should be programmed with care, bearing in mind the potential psychological burden. For example, in tetralogy of Fallot, monomorphic ventricular tachycardia may be amenable to antitachycardia overdrive pacing. Programming higher defibrillation detection thresholds and/or prolonging time to detection may further prevent unnecessary shocks. Technical challenges to ICD lead implantation may be unique. When vascular access limitations preclude transvenous leads or when thromboembolic risks are prohibitive, epicardial systems may be required. These approaches require some creativity and an understanding of anatomy and defibrillation vectors. Epicardial patches have largely been abandoned due to complications such as pericardial restriction. In a multicenter series that assembled 22 predominantly pediatric patients with ICDs devoid of transvenous shocking coils or epicardial patches, configurations included subcutaneous arrays and epicardially or subcutaneously placed transvenous ICD leads.37 High defibrillation thresholds were noted in 18%, and 32% required system revision over a follow-up of 2 years.37 More recently, a computer-based assessment tool was developed with imagebased finite element modeling to compare electric fields and projected defibrillation thresholds with different configurations.38 A variety of extracardiac orientations were predicted by changing anatomic relations and varying electrode lengths. Among the important observations, can placement
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Figure 4 Transvenous cardiac resynchronization therapy in congenital heart disease. A transvenous biventricular ICD system was implanted in a patient with congenitally corrected transposition of the greater arteries and dextrocardia. Right (A) and left (B) anterior oblique views are depicted. The ICD lead was placed in the subpulmonary left ventricle (LV). A lead was inserted in the coronary sinus to pace the subaortic right ventricle (RV). RA ⫽ right atrium.
opposite rather than ipsilateral to a subcutaneous electrode resulted in lower defibrillation thresholds.38 Such an interactive image-based approach may prove helpful in guiding individualized lead placement when standard approaches are contraindicated.
Cardiac resynchronization therapy In adults with congenital heart disease, major challenges in cardiac resynchronization therapy include patient selection, technical issues related to lead placement, unique forms of dyssynchrony, and means of assessing outcomes. Traditional indications are derived from multiple randomized clinical trials and consist of systemic left ventricular systolic dysfunction, a wide QRS interval, and New York Heart Association (NYHA) class 3 or 4 symptoms despite optimal medical therapy. In contrast, supportive evidence for cardiac resynchronization therapy in congenital heart disease is limited to case series and small crossover studies in the acute postoperative setting.39,40 Notably, NYHA functional classification should be interpreted with caution in adults with congenital heart dis-
Figure 5 Hybrid approach to cardiac resynchronization therapy in congenital heart disease. A transvenous ICD lead was positioned in the subpulmonary left ventricle in a patient with congenitally corrected transposition of the great arteries, prosthetic right-sided AV valve, and permanent slow atrial fibrillation. Partial atresia of the coronary sinus ostium precluded transvenous lead placement for cardiac resynchronization therapy. Via a minithoracotomy incision, an epicardial lead was sutured to the lateral free wall of the subaortic right ventricle (arrows). Anteroposterior (A) and lateral (B) chest x-ray views are displayed.
ease. Despite an alleged paucity of symptoms that reflects adaptation to a lifelong disorder, exercise capacity is generally depressed in a manner comparable to chronic heart failure.41 The heterogeneity of the patient population and singular anatomies encountered further obscure the selection of appropriate candidates. Whereas standard indications rely on QRS duration as a marker of dyssynchrony, most case series in congenital heart disease incorporate some echocardiographic metric. No uniform approach has yet emerged. Pending prospective validation, imaging studies such as tissue Doppler, strain, strain rate, three-dimensional echocardiography, and/or tissue tracking may prove valuable in guiding the selection of potential responders. In spite of these challenges, studies have begun addressing various potential substrates for cardiac resynchronization therapy in congenital heart disease. These include the more prevalent right as opposed to left bundle branch block pattern, dysfunction of a subpulmonary right ventricle, systemic right ventricular dysfunction in patients with transposition of the great arteries, multisite pacing for dyssyn-
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chrony of the univentricular heart, and acute postoperative ventricular failure. A few case series have reported favorable long-term outcomes, although analyses are subject to nonblinded assessment, confounding by concomitant surgical interventions, and lack of control groups to adjust for spontaneous improvement or response to medical therapy.39,40,42 Notwithstanding these limitations, provocative observational data suggest a low rate of nonresponders and major successes in delisting patients with advanced forms of heart failure from transplant programs, particularly in the youngest subgroups.40 Implantation strategies remain empiric. In the absence of contraindications, transvenous lead systems are generally preferred when the anatomy is favorable, including coronary sinus drainage into an accessible systemic venous atrium. Lead positioning may be particularly challenging (Figure 4). In certain circumstances, such as complete transposition of the great arteries with intraatrial baffle redirection or congenitally corrected transposition with a malformed or underdeveloped coronary sinus, a hybrid approach may be required (Figure 5). Atrial and subpulmonary ventricular leads may be inserted transvenously, with a minithoracotomy to place an epicardial systemic ventricular lead. If associated with an ICD, the defibrillator lead remains intracardiac with such an approach, which is gener-
Figure 6 Catheter ablation of an arrhythmia substrate partially covered by prosthetic material. Electrophysiologic study and catheter ablation were performed in a patient with Ebstein’s anomaly, one and a half ventricular repair (bidirectional Glenn shunt), and prosthetic tricuspid valve. A: Angiography of the right atrium in the anteroposterior view. Note the tricuspid valve prosthesis and absent right atrium to superior vena cava connection. B: Electroanatomic map in a left lateral view. Local activation times are color coded, with the wavefront spreading from white to red, orange, yellow, green, light blue, dark blue, and purple. A counterclockwise circuit revolving around the prosthetic tricuspid valve is appreciated. The site of successful irrigated radiofrequency catheter ablation that produced bidirectional isthmus block is shown in right (C) and left (D) anterior oblique view. Arrows indicate the catheter position along the inferior portion of the tricuspid valve prosthesis.
1469 ally associated with lower defibrillation thresholds.38 Finally, an entirely epicardial system may be implanted, with care to position leads remote from one another, in areas of late electromechanical activation.39,40
Catheter ablation In contrast to the limited albeit occasionally effective role of medical therapy, advances in three-dimensional mapping techniques and catheter technologies have provided new optimism for arrhythmia management in adults with congenital heart disease. With a thorough understanding and appreciation for underlying structural disease, surgical barriers, tenuous physiology, and variations in conduction system anatomy, most arrhythmias can be safely and successfully ablated.43 Careful preprocedural planning may include a detailed review of operative notes and all documented arrhythmias, visualization of three-dimensional anatomy by cardiac magnetic resonance imaging or computed tomographic scan, and ensuring qualified anesthesiology assistance, availability of “air filters” for intravenous lines, and accessibility to an intensive care unit bed postintervention. A typical procedure consists of importing cardiac magnetic resonance or computed tomographic images into a three-dimensional mapping system, performing angiography of the desired chamber, hemodynamic assessment if
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Figure 7 Electroanatomic mapping in a right atrium to pulmonary artery Fontan. An electroanatomic map (left) and imported cardiac magnetic resonance image (right) are shown in a patient with a classic modified Fontan and recalcitrant atrial tachyarrhythmias. Gray regions denote areas of dense scar. Local activation times are color coded, from white to red, orange, yellow, green, light blue, dark blue, and purple. Note the narrow channel of tissue between two dense scars. The arrhythmia circuit propagated counterclockwise around the upper scar and was successfully interrupted by ablating this narrow isthmus. CSO ⫽ coronary sinus ostium; IVC ⫽ inferior vena cava.
indicated, baseline electrophysiologic testing, induction of a clinically relevant arrhythmia if not spontaneously present, three-dimensional mapping of local activation times and barriers to conduction, use of standard techniques such as entrainment mapping to confirm the diagnosis and desired target site, actual ablation, and demonstration of lesion effectiveness. Particular challenges are numerous, not least of which is the operator resilience required for lengthy procedures. Vascular access may be compromised by prior venous cutdowns and/or multiple interventions during childhood. When venous access is limited, esophageal leads may be considered to record atrial electrograms. The chamber of interest may be formidably large, as in right atrium to pulmonary artery Fontan connections, with difficulties ensuring optimal catheter contact and transmural lesions. Baffle or conduit obstructions and acute angles may impede access to areas of interest. A stable reference catheter position may be problematic, especially when the coronary sinus is not accessible. We commonly use screw-in leads when such a situation arises. Punctures across conduits or surgical patches may be required, as for transposition of the great arteries with intraatrial baffles, univentricular hearts with total cavopulmonary connections, and surgically repaired atrial septal defects. Occasionally, arrhythmia substrates are concealed beneath patches or prosthetic material (Figure 6). Although desired tissue penetration may not be feasible, in our experience, the greatest success is achieved with irrigated radiofrequency ablation guided by precise mapping.44 Other challenges include localization of relevant anatomic structures, such as the right AV groove in Ebstein’s anomaly, avoidance of inadvertent damage to displaced conduction systems,45 and deciphering complex or multiple arrhythmia circuits. Recurrences and/or onset of new ar-
rhythmias postablation appear highest in patients with Fontan palliation for univentricular hearts.46 Single circuits may be present, with potential for long-term arrhythmia-free survival (Figure 7). By and large, quality of life is substantially improved following catheter ablation.46
Current controversies There are several ongoing controversies in arrhythmia management patterns for adults with congenital heart disease. To highlight but a few, opinions diverge as to whether transvenous or epicardial atrial leads should be favored in Fontan patients. Thrombus formation on pacing leads is an important concern given the multiple clotting factor abnormalities, increased platelet reactivity, and sluggish circulation. In the absence of a subpulmonary ventricular pump to overcome increases in afterload engendered by pulmonary emboli, hemodynamic consequences may be devastating. Indeed, in adults with univentricular hearts, thromboembolism in the Fontan pathway/pulmonary circulation is a leading cause of death.47 Whereas some recommend avoidance of transvenous leads in this context, proponents generally support long-term antiplatelet or anticoagulation therapy. Another area of controversy involves the interaction of arrhythmias in determining timing of pulmonary valve replacement in tetralogy of Fallot and the impact of surgery on modifying risk for sudden death. In patients with ventricular arrhythmias and severe pulmonary regurgitation, pulmonary valve replacement may result in hemodynamic and symptomatic improvement. However, most caregivers agree that pulmonary valve replacement alone does not fully address the underlying arrhythmic substrate. Whether directed or empiric concomitant surgical ablation provides sufficient protection against sudden death remains uncertain.48,49 In one series of patients with repaired tetralogy of Fallot, ventricular tachycardia recurred in 10% despite sur-
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gical ablation.50 Similar concerns about recurrent ventricular tachycardia and risk for sudden death are central to the debate regarding transcatheter ablation as primary therapy for sustained ventricular tachycardia in tetralogy of Fallot, in the absence of an ICD.51 Another contentious issue in the arrhythmia management of adults with congenital heart disease is the role of catheter ablation vs Fontan conversion to a total cavopulmonary connection with adjuvant surgical ablation (i.e., modified right atrial maze with or without a Cox maze III) in patients with right atrium to pulmonary artery anastomoses.47,52 Perspectives differ as to whether surgery should be considered primary therapy for atrial arrhythmias in the absence of underlying hemodynamic lesions, such as Fontan obstruction.53 Proponents of a primary surgical approach call attention to the markedly dilated and hypertrophied right atrium with reservations about transmurality and contiguity of linear catheter ablation lesions, high recurrence rates postablation, low perioperative mortality (1%), infrequent late deaths (5%), and an 86% freedom from atrial reentrant tachyarrhythmias at 5 years.54 In patients without other indications for Fontan conversion, supporters of transcatheter ablation for atrial arrhythmias emphasize its less invasive nature, very low associated morbidity and mortality, potential for long-term arrhythmia-free survival in some, reduction of arrhythmia burden with improved quality of life in most, ease of repeat intervention if required, and the fact that catheter ablation does not preclude later surgical intervention for refractory arrhythmias.18,43,46 Moreover, higher perioperative mortality rates (5%–10%) are cited,47,55,56 as is the lack of controlled studies demonstrating a net benefit of a widely applied first-line surgical approach. These ongoing controversies underscore recommendations to concentrate the care of adults with congenital heart disease within regional centers supported by collaborative multidisciplinary teams dedicated to improving outcomes, education, and research.53,57 Electrophysiology personnel with specific skills and knowledge in congenital heart disease should be integrated in such teams and provide the full range of ablative and device therapies, in addition to consultative and diagnostic services appropriate to the special needs of patients with adult congenital heart disease.57
Conclusion Dedicated clinics, research, guidelines, and associations now are acknowledging that adults with congenital heart disease compose a distinct population of patients with unique needs and concerns. Arrhythmias in adults with congenital heart disease constitute a burgeoning branch of electrophysiology, with an arguably unprecedented degree of diversity. The skill set required to maximize patient safety and optimize procedural outcomes involves merging electrophysiology proficiencies with a thorough understanding of congenital heart disease anatomy and physiology. This special area of interest is increasingly recognized in a formalized context. Arrhythmia management guidelines
1471 have begun incorporating issues relevant to this patient population, and targeted training programs are offered. At our institution, an adult congenital arrhythmia clinic was inaugurated in 2004. Although electrophysiology challenges in adults with congenital heart disease are substantial, so too is the potential to impact on quality of life and long-term survival.
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