CONTEMPORARY REVIEW

Sudden death in adult congenital heart disease: Risk stratification in 2014 Edward P. Walsh, MD, FHRS From the Cardiac Electrophysiology Division, Boston Children’s Hospital, Boston, Massachusetts, and Harvard Medical School, Boston, Massachusetts. Arrhythmias and sudden death continue to plague a subset of adult patients with congenital heart disease. Despite investigative efforts spanning many decades, accurate identification of the high-risk patient remains challenging owing to a limited population size, relatively low event rate, and constantly evolving surgical approaches to the various malformations. Furthermore, until recently, most studies of the subject involved singlecenter formats with limited statistical power. The number of adult survivors has now reached a critical size where larger collaborative projects are beginning to generate more objective criteria for assessing risk. This review will provide an update on risk stratification for several of the major congenital cardiac lesions and outline the current recommendations for surveillance and management.

Introduction The late 1930s marked the beginning of a remarkable series of surgical advances for congenital heart disease (CHD) that permitted long-term survival for a unique group of patients who would otherwise have died during early childhood.1 Improved longevity would eventually expose a number of unanticipated late complications, central among which were atrial and ventricular arrhythmias contributing to sudden cardiac death (SCD). Wolff et al2 were the first to sound the alarm in 1972 when they published observations on disrupted conduction patterns and ventricular tachycardia (VT) associated with SCD in patients who have undergone repair of tetralogy of Fallot. Since then, the topic of late arrhythmias has received the attention of all cardiologists involved with the longitudinal care of this growing population. Arrhythmias in CHD arise from the abnormal myocardial substrate caused by variable pressure/volume loads, cyanosis, and certain anatomic features specific to the individual structural lesion. The situation is further complicated by palliative or corrective surgery, creating myocardial scars that can function as conduction barriers and central obstacles for macroreentrant circuits. Of note, the most malignant Address reprint requests and correspondence: Dr Edward P. Walsh, Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. E-mail address: [email protected]. edu.

1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.

KEYWORDS Congenital heart disease; Sudden cardiac death; Ventricular tachycardia; Implantable cardioverter-defibrillator ABBREVIATIONS CHD ¼ congenital heart disease; D-TGA ¼ D-looped ventricles and transposition of the great arteries; EPS ¼ electrophysiology study; ICD ¼ implantable cardioverterdefibrillator; L-TGA ¼ L-looped ventricles and transposition of the great arteries; LV ¼ left ventricle/ventricular; PACES ¼ Pediatric and Congenital Electrophysiology Society; SCD ¼ sudden cardiac death; RV ¼ right ventricle/ventricular; TGA ¼ transposition of the great arteries; VT ¼ ventricular tachycardia (Heart Rhythm 2014;11:1735–1742) All rights reserved.

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arrhythmias in the CHD population typically do not become manifest until the third decade of life or beyond, suggesting that a period of degenerative remodeling also plays a role in their genesis. For this reason, SCD looms as a far greater concern once CHD patients reach adulthood than it did during childhood and adolescence.

Magnitude of the problem The number of adults with CHD living in North America is now estimated to exceed 1 million. Included in this group are some cases with relatively minor disease in whom arrhythmia risk is known to be low (eg, repaired atrial septal defect or ligated ductus arteriosus), but the majority can be classified as having moderate or severe malformations3 with the potential for life-threatening rhythm disturbances. In several large series examining long-term outcomes after CHD surgery, sudden unexpected events (usually arrhythmic, but occasionally vascular or thrombotic) ultimately accounted for 20% or more of the total mortality in patients with complex lesions.4–6 Three important articles have provided detailed data on the overall SCD risk in large populations with CHD. Silka et al7 examined outcomes for patients from the state of Oregon who underwent CHD surgery between 1958 and 1996 and identified sudden arrhythmic death in 30 individuals from a cohort of 3589. When event rate was adjusted http://dx.doi.org/10.1016/j.hrthm.2014.07.021

1736 according to specific lesion type and follow-up duration, the incidence appeared highest for adult patients with transposition of the great arteries (TGA) and a systemic right ventricle (RV) after atrial baffling operations, followed by those with left ventricular (LV) outflow obstruction (aortic stenosis or coarctation of the aorta), followed by those with tetralogy of Fallot. A different study format was used by Koyak et al8 in their multinational case-control study of more than 25,000 adult CHD patients that included surgical follow-up as well as natural history of nonoperable cases. They identified 171 cases of SCD due to arrhythmias within this large group. Denominators were not reported for specific lesion type to allow calculation of incidence, but the conditions with the highest number of SCD events included Eisenmenger syndrome, TGA with a systemic RV, and tetralogy of Fallot. More recently, Gallego et al9 reported their single center experience of more than 3000 adult patients with CHD, in which patients with TGA and a systemic RV were again the highest risk group, followed by those with a single ventricle. These studies are among the few that have looked at SCD among CHD patients in a global sense, and all 3 arrived at nearly identical conclusions: (1) malignant arrhythmias will occur in 1% of all patients with some form of CHD over a mean follow-up period of 10 years, (2) these events will be largely concentrated in adult aged patients with complicated hemodynamic lesions for whom the SCD risk may reach 10% per decade of follow-up, and (3) abnormal “systemic” ventricular function (whether this involves an anatomic RV or LV) is among the strongest predictors of malignant arrhythmias. Most other studies of the SCD issue in CHD tend to focus on a specific lesion, with an understandable predilection to choose a common malformation with an effective surgical solution and a large number of patients surviving into middle age. Hence, tetralogy of Fallot has been studied more extensively than any other condition, and so the mechanisms for SCD and its risk factors have been worked out reasonably well. Knowledge is less developed for other forms of CHD, such as TGA or single ventricle, either because the malformation is less common or because survival into adulthood is limited. The best available data suggest that it is hazardous to assume that lessons learned from tetralogy of Fallot are applicable to other forms of CHD. Only recently has multicenter attention been directed to SCD in alternate lesions, and risk stratification for such patients appears to differ in some important ways. It is useful, therefore, to evaluate arrhythmia risk in adult CHD on a lesion-by-lesion basis.

Heart Rhythm, Vol 11, No 10, October 2014 that can potentially support macroreentry circuits near the outflow tract11–13 and that traditional surgical repair might reinforce this potential (Figure 1). Patients with tetralogy can also develop RV and LV dysfunction from hemodynamic stress, putting them at additional risk of more disorganized polymorphic VT and ventricular fibrillation, similar to arrhythmias seen in any other form of dilated cardiomyopathy. Beyond the VT risk, these patients also carry a heavy burden of atrial macroreentrant tachycardias14,15 involving the cavotricuspid isthmus and/or atriotomy scars (Figure 2). Atrial tachycardia, when conducted rapidly in a patient with tetralogy and depressed ventricular function, can contribute to the SCD risk in some individuals. More than 100 studies have been published examining SCD in repaired tetralogy since the mid-1970s. The largest of these permit estimation of the SCD risk in a given cohort with tetralogy of approximately 2% per decade of followup.7,16–19 This figure, however, is based on study groups that include both pediatric and adult subjects with variable follow-up duration. If attention is directed exclusively to adult patients 25 years or more after surgical repair, the SCD risk rises to the range of 6%–10% per decade of followup.17,19 The search for risk factors predicting VT and SCD in patients with tetralogy has generated an extensive catalog that includes patient age, surgical timing/technique, measures of hemodynamic status, electrocardiographic findings, noninvasive rhythm monitoring, and invasive electrophysiologic evaluation. The sheer length of the list reflects the challenge of working with a limited population size and low event rate, but perhaps the biggest obstacle to a strong

PA

VSD

Conal Septum

Risk assessment in specific CHD lesions Tetralogy of Fallot The mechanism of SCD in tetralogy of Fallot has been under investigation for more than 4 decades. Early on there was concern that atrioventricular block accounted for these events,2 but it quickly became evident that VT was the culprit in most cases.10 It is now understood that the intrinsic anatomy of the RV in tetralogy involves structural features

Figure 1 Pathologic specimen from a young patient with unrepaired tetralogy of Fallot demonstrating the intrinsic anatomic features that can contribute to macroreentrant ventricular tachycardia. A portion of the anterior right ventricle (RV) has been removed to expose the ventricular septal defect (VSD), the stenotic pulmonary outflow tract (PA), and the narrow band of muscle (Conal Septum) running between the VSD and the PA. The 3 curved arrows mark locations that could function as protected corridors supporting macroreentry after surgical repair.

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Figure 2 Electroanatomic maps of the right atrium demonstrating atrial macroreentry that developed in an adult with tetralogy of Fallot many years after surgical repair. Surgery included a right lateral atriotomy incision (hatched area). A: Typical counterclockwise macroreentry around the tricuspid valve (TV) through the cavotricuspid isthmus. B: Second macroreentry circuit on the lateral atrial wall that used the atriotomy scar as the central obstacle and traveled through a narrow gap between the lower edge of the scar and the inferior vena cava (IVC).

predictive model is that the surgical approach to tetralogy has evolved substantially through the years. Patients managed from the 1940s through the 1970s were likely to receive initial palliation with a systemic pulmonary shunt procedure that imposed a volume load on the LV and delayed definitive repair. This was largely supplanted in the 1980s by complete repair during infancy,20,21 but early techniques for infant repair often involved a large transannular patch, resulting in chronic pulmonary regurgitation and eventual RV enlargement. Surgery for the current generation of tetralogy patients still favors early complete repair, but now stronger efforts are made to preserve pulmonary valve competence and minimize the size of right ventriculotomy incisions.22 To complicate matters further, late reintervention for transcatheter or surgical pulmonary valve replacement has become commonplace for older patients with tetralogy, and the electrophysiologic consequences of late valve replacement are still uncertain.23,24 It is reasonable to assume that the incidence and mechanisms of SCD may differ among all these subgroups. Nonetheless, certain risk factors tend to show up with high regularity in recent studies regardless of surgical history, and these have now become widely accepted as the variables of greatest interest for risk stratification in tetralogy (Table 1). RV size and function have always featured prominently in risk analysis for this group.19,25,26 Although residual pulmonary stenosis or ventricular septal defect are now unusual after

tetralogy corrections, pulmonary regurgitation remains a common sequela that will contribute to volume overload and RV dysfunction. Multiple studies confirm that RV enlargement27 will elevate the VT and SCD risks. Gatzoulis et al28 were the first to demonstrate the close correlation between QRS duration and RV size. From their data and several subsequent studies, the risk of SCD events increases whenever the RV is severely enlarged and QRS duration reaches or exceeds 180 ms. Depressed RV systolic function also appears to confer higher risk,29 as does the finding of extensive RV fibrosis detected by magnetic resonance imaging.30 Table 1 Risk factors after repair of tetralogy of Fallot  Older age at the time of complete repair  Longer duration of follow-up since complete repair  History of syncope or rapid palpitations  Severe pulmonary regurgitation  Severe RV enlargement  Moderate to severe RV systolic dysfunction  Extensive RV fibrosis  Moderate-severe LV dysfunction  Elevated LV end-diastolic pressure  QRS duration Z180 ms  Nonsustained VT on the Holter monitor  History of atrial tachycardia  Inducible VT at EPS EPS ¼ electrophysiology study; LV ¼ left ventricular; RV ¼ right ventricular; VT ¼ ventricular tachycardia.

1738 Contemporary analysis of tetralogy risk has begun to shift away from exclusive RV evaluation to include more emphasis on LV function. Evidence is now accumulating that LV dysfunction may in fact be a better discriminator for high-risk status than traditional RV variables. No doubt there is a strong component of RV-LV interaction at work in patients with tetralogy,31 but several measures of LV performance have been convincingly linked to risk. Khairy et al32 looked at discharge rate of implantable cardioverterdefibrillators (ICDs) in a large group of patients with tetralogy and found LV end-diastolic pressure to be the strongest predictor of appropriate shock. Similarly, Diller et al33 found that echocardiographic measures of LV function could enhance predictive accuracy when combined with RV functional measures. A recently completed multicenter study from the Pediatric and Congenital Electrophysiology Society (PACES) found that moderate to severe LV systolic dysfunction on the echocardiogram was a stronger predictor of serious events than any RV variable across all surgical eras.34 The results of these and other studies35 serve to emphasize the importance of systemic ventricular performance in CHD, even when the hemodynamic and surgical stress is ostensibly weighted toward the subpulmonary ventricle. Noninvasive rhythm monitoring for ventricular ectopy burden has long been used as part of risk stratification, but because ectopy is rather ubiquitous in the adult population with tetralogy,36 there has always been concern regarding its specificity. Czosek et al37 recently reported that nonsustained VT (4 or more beats) on the Holter monitor was indeed associated with sudden cardiac events in adults after tetralogy repair, while lower grades of ectopy (frequent isolated beats, couplets, and triplets) were not. A history of atrial tachycardia has also been shown to be associated with a higher risk of VT and death in older patients with tetralogy.29 Specificity is again called into question since 20% or more of adult patients with tetralogy may have atrial flutter and/or fibrillation,38,39 and there are undeniably strong links to hemodynamic variables such RV function, tricuspid regurgitation, and atrial size. Whether atrial tachycardia warrants attention as an independent variable remains uncertain, but it does appear useful when viewed in the context of RV hemodynamics. Often overlooked or unreported in many studies of SCD in tetralogy is the simple matter of historical symptoms in advance of a malignant event. A report from Koyak et al40 recently highlighted the importance of patient symptoms for risk stratification by demonstrating that a history of symptomatic (but not asymptomatic) nonsustained VT was the single best predictor of subsequent appropriate ICD discharge in their patients. Similarly, the multicenter PACES trial found that a history of syncope and/or rapid palpitations was the single most powerful item in differentiating high-risk patients from low-risk patients.34 No matter which risk factor is chosen from the studies published to date, the positive predictive accuracy for any single item can only be described as “modest.” Even QRS

Heart Rhythm, Vol 11, No 10, October 2014 duration, which for a time was considered by many to indicate high-risk status whenever it exceeded 180 ms, has subsequently been shown to have limitations when analyzed in some other study groups.41 The uncertainty surrounding noninvasive risk assessment led some investigators to explore the merits of an invasive electrophysiology study (EPS) incorporating programmed ventricular stimulation. The single center study by Alexander et al42 and the subsequent multicenter study by Khairy et al43 both confirmed that inducible VT at EPS correlated strongly with allcause mortality at 5-year follow-up, while a negative study was reassuring. It must be emphasized that in both these reports, patients were selected for invasive study on the basis of symptoms, poor hemodynamics, Holter findings, or other concerns. Ventricular stimulation at EPS has not been used, nor is it recommended, as a routine screening tool. Rather, EPS may be a useful way to refine risk stratification in patients when 1 or more noninvasive risk factors are detected. Despite these many attempts to perfect risk stratification in adult tetralogy patients, the process remains challenging. Efforts are now underway to develop and test prediction models based on some combination of risk factors, with weighted values assigned to each variable, and determine prospectively whether an accurate “risk score” system can be generated.32,34,39,40

TGA Survival for patients born with D-looped ventricles and TGA (D-TGA) was nearly impossible beyond infancy until the Senning and Mustard operations were introduced in the late 1950s and early 1960s. However, the price paid for successful surgery was high if and when these patients reached adulthood, since many had sinus node dysfunction, recurrent atrial tachycardias, and a systemic RV that often failed. Once methods were perfected in the 1980s for direct switch of the great arteries, atrial baffling for D-TGA became largely obsolete, but there is still a sizable population of adults contending with the late complications of the older surgical approach. A different but related group of patients are those born with L-looped ventricles and TGA (L-TGA, or so-called “congenitally corrected” transposition). Although patients with L-TGA are not dependent on urgent surgery to correct cyanosis after birth, they nevertheless suffer from long-term disabilities of a systemic RV and rhythm concerns. There is a disturbing incidence of SCD for patients with both D-TGA and L-TGA. In several large series, the risk of SCD was higher for these groups than for any other form of CHD. Studies of SCD in patients with transposition have concentrated primarily on the D-TGA group after atrial baffling surgery. A report from New Zealand on outcomes after the Mustard operation found an SCD rate of 10% and an all-cause mortality of 20% after 15 years of follow-up.44 Kammeraad et al45 studied risk factors after Senning and Mustard operations in 47 SCD cases matched to controls.

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They found that arrhythmia symptoms and a history of atrial tachycardia increased risk, but there were no electrocardiographic or Holter markers to distinguish the SCD group. VT or ventricular fibrillation was documented in 21 of 47 patients, but whether these were initiating events or terminal rhythms is uncertain. There are certainly well-documented episodes of rapidly conducted atrial tachycardia progressing to cardiac arrest in this patient group,46 so it is likely that atrial arrhythmias play a role in at least some of these abrupt fatalities. In contrast to the tetralogy experience, programmed ventricular stimulation does not seem to be informative in D-TGA. Patients who had undergone Mustard or Senning and who received a primary prevention ICD based on positive ventricular stimulation studies are unlikely to receive appropriate shocks from their device.47 Although EPS plays an important role in the mapping and ablation of atrial tachycardia for this population,48 ventricular stimulation is performed infrequently nowadays for risk assessment. This is not to say ventricular arrhythmias can be ignored.49 VT is still a concern and can necessitate ICD placement in patients with advanced dysfunction of their systemic RV,50 but it remains uncertain what criteria justify primary prevention implants. Ventricular ectopy burden evaluated using Holter monitoring did not predict events for D-TGA patients in the studies by Kammeraad et al45 or by Czosek et al.37 Schwerzmann et al49 had suggested that a QRS duration above 140 ms was a potential marker of patients at risk of VT after Mustard operation, but this variable has yet to be verified in broader studies. The generally accepted risk factors for sudden arrhythmic death in this population are summarized in Table 2. Attrition from death and transplant is now shrinking the population of patients with D-TGA who were repaired using an atrial baffle, and it is unlikely that more robust analysis of SCD risk factors will be forthcoming. The most practical approach at present seems to be aggressive therapy for atrial tachycardia, with primary prevention ICD therapy reserved at the discretion of the cardiologist for patients with the most severe degrees of RV dysfunction. Even less is known about SCD in patients with L-TGA and a systemic RV. It is clear that they are intrinsically prone to a unique set of rhythm concerns including spontaneous atrioventricular block owing to congenitally abnormal conduction tissues51 and accessory pathways along the left-sided tricuspid valve,52 but these 2 issues are certainly manageable in the present era with pacemaker and catheter ablation therapy. Still, the SCD rate remains high in adults with this condition. In the multinational case-control study by Koyak et al,8 9 of the 12 patients with L-TGA who died suddenly had complicated anatomy with secondary structural issues

Table 2 Risk factors after atrial switch for transposition  Longer duration of follow-up  History of syncope or rapid palpitations  Atrial tachycardia  Depressed systemic right ventricular function

1739 such as ventricular septal defect or an Ebstein type malformation of their tricuspid valve that contributed to systemic RV dysfunction over time. Furthermore, there is evidence that coronary perfusion of the systemic RV is suboptimal and can further compromises RV function in this setting.53 Although the mechanism of SCD in patients with L-TGA is uncertain and may have a mixed etiology, most data point toward ventricular arrhythmias caused by a myopathic systemic RV.54

Single ventricle Introduction of the Fontan operation in the early 1970s for the first time allowed reasonably effective hemodynamic palliation for patients with complex univentricular physiology. Surviving patients faced many challenges, and as the vanguard entered adolescence and adulthood in the 1980s– 1990s, it became apparent that arrhythmias, heart failure, and thromboembolic events would be major long-term management concerns.55 Macroreentrant atrial tachycardia is the most common arrhythmia seen in this patient group. The consequences of atrial tachycardia can be profound at several levels. Besides the stress of rapid rates and loss of effective synchrony, it can be a potent trigger for thrombus formation within the nonpulsatile flow through the right heart in Fontan circulation. The risk of developing atrial tachycardia approached 50% for patients who underwent older-style Fontan surgery using a connection between the right atrium and the pulmonary artery.56 This early technique resulted in a dilated right atrial chamber, thick atrial muscle, and the potential for multiple sites of macroreentry.57 Surgical modifications were eventually introduced to allow a more direct connection between caval blood flow and the pulmonary arteries using the lateral tunnel or extracardiac conduit techniques, and subsequent to this change, the incidence of atrial tachycardia decreased dramatically to less than 10% during equivalent follow-up.58 The link between atrial tachycardia and SCD in patients who have undergone the Fontan procedure is not firmly established, though all clinicians involved with these patients will recognize that these arrhythmias are poorly tolerated and contribute significantly to morbidity and mortality.59 Atrial tachycardia is associated with older surgical techniques, longer duration of follow-up, and the presence of sinus node dysfunction.60 Atrial fibrillation may also be seen, though it is less common.61 Primary ventricular arrhythmias have not been studied well in single ventricle patients, but may also be operative in some cases of SCD. Holter monitoring done as part of the study by Czosek et al37 found moderate to high grade ectopy in about 25% of their subgroup with single ventricle, but the presence of nonsustained VT was not predictive of SCD. Generally accepted risk factors for sudden arrhythmic death in this population are summarized in Table 3, but there is still much to be learned about the precise causes. Single ventricle patients present major challenges whenever pacemaker or ICD therapy is contemplated. Although

1740 Table 3 Risk factors after the Fontan operation  Longer duration of follow-up  History of syncope or rapid palpitations  Older Fontan technique (atriopulmonary connection)  Atrial tachycardia  Depressed single ventricular function

atrial leads can sometimes be implanted by a transvenous route,62 ventricular pacing leads and ICD shock leads require an epicardial approach.63 Subcutaneous ICD placement may be another option, but the experience with this new technology remains limited in CHD, and there are still uncertainties regarding sensing function in such patients.64 These technical difficulties have resulted in a rather small number of patients with single ventricle receiving primary prevention ICDs, limiting our ability to identify mechanisms of SCD and test risk-stratification schemes for the group.

Congenital aortic stenosis and other left heart obstructive lesions The second natural history study of CHD published in 1993 was the first large series to quantitate the risk of SCD in patients with congenital LV outflow obstruction.65 There were 44 cardiac deaths reported in the original cohort of 462 patients, 25 of which were sudden and unexpected. These events were confined almost exclusively to patients who had a gradient of 450 mm Hg and had been followed for more than 15 years. A positive history of symptoms (angina, dyspnea on exertion, and Z2 episodes of syncope) was a strong predictor of all-cause mortality. Holter monitoring data were available for 117 of the survivors.66 More than 10% had nonsustained VT recorded that correlated with higher LV end-diastolic pressure, the presence of aortic regurgitation, and a history of aortic valve replacement. Shortly after this article, a similar rate of sudden arrhythmic death was reported for patients with aortic valve disease by Silka et al,7 and most of the SCD cases were characterized as having significant residual aortic stenosis or insufficiency. It was a surprise (and concern) that multiple instances of SCD were also observed among patients who had undergone surgery for coarctation in the Silka series. Data were not available to ascertain whether these cases had residual arch narrowing and/or systemic hypertension, but “profound” ventricular hypertrophy was mentioned in most of the fatalities. Generally accepted risk factors for sudden arrhythmic death in this population are summarized in Table 4. These data have been logically interpreted as implicating LV hypertrophy and diastolic stiffness as the principal risk factors for SCD in congenital LV outflow obstruction. It follows that early efforts to eliminate or minimize these gradients may prevent the hypertrophic remodeling and fibrosis responsible for the development of malignant ventricular arrhythmias. Surgical and catheter interventions have certainly become more effective in accomplishing this goal, and the results seem optimistic thus far. A 2010 report

Heart Rhythm, Vol 11, No 10, October 2014 by Brown et al67 reviewed a group of more than 500 young patients with aortic valve disease treated by transcatheter balloon dilation and followed for a mean period of 12 years, with only 1 case of SCD outside the infant age group.

Recommendation for risk assessment in adult CHD An expert consensus document from the PACES and Heart Rhythm Society was recently completed to address recognition and management of arrhythmias in adults with CHD.68 All efforts were made by the writing committee to acknowledge data deficiencies in this field and avoid dogmatic recommendations on controversial topics. The following are selected Class I or Class IIa recommendations abstracted from the document that are most relevant to the issue of risk stratification: a) Arrhythmia care for adult CHD should be delivered at regional centers with specialized staff having a full understanding of the anatomy, surgical history, and medical needs of this patient group (Class I). b) Careful history for arrhythmia symptoms, and thorough assessment of hemodynamic status, are essential for intelligent decision making in CHD patients (Class I). c) Invasive electrophysiologic testing is indicated in adult CHD patients with unexplained syncope and “high risk” substrates that are known to be associated with VT or poorly tolerated atrial tachycardias (Class I). d) Periodic Holter monitoring can be beneficial as part of routine follow-up in asymptomatic patients (Class IIa). e) Invasive EPS can be useful in risk stratification in adults with tetralogy of Fallot and additional noninvasive risk factors (Class IIa). Committee recommendations for ICD placement largely echo the established guidelines for device therapy in adults with more conventional forms of heart disease: a) ICD therapy is indicated in adults with CHD who are survivors of cardiac arrest after reversible etiologies have been excluded (Class I). b) ICD therapy is indicated in adults with CHD and spontaneous sustained VT after careful hemodynamic and electrophysiologic assessment, though catheter ablation or surgery may be a reasonable alternative or adjunct in selected patients (Class I). Table 4 Risk factors in LV outflow obstruction  Longer duration of follow-up  History of Z2 episodes of syncope  Outflow gradient 450 mm Hg  Aortic regurgitation  High LV end-diastolic pressure  Depressed LV systolic function  Severe LV hypertrophy LV ¼ left ventricular.

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c) ICD therapy is indicated in adults with CHD and a systemic ventricular ejection fraction less than or equal to 35%, biventricular physiology, and NYHA class II or III symptoms (Class I). d) ICD therapy is reasonable in selected adults with tetralogy of Fallot and multiple risk factors such as LV dysfunction, nonsustained VT, QRS Z 180 msec, extensive RV scarring, or inducible sustained VT at EPS (Class IIa). It is important to emphasize that ICD implant in patients with CHD can involve unique technical challenges related to vascular access and lead positioning,69 as well as thromboembolic concerns.70 Device implantation in patients with complex lesions should be attempted only in experienced centers. High-stakes decisions for complex patients with rare diseases must frequently be made without the benefit of large clinical trials as a guide, and arrhythmia care for the adult CHD population still relies heavily on individualized patient assessment. However, even though data remain limited in many areas, we continue to learn from our triumphs and failures to push this field forward. It is reasonable to expect that the incidence of SCD in adults with CHD will decrease with ongoing improvements in risk analysis, more effective therapy, and intelligent modifications in surgical techniques.

References 1. Gross RE. Surgical management of the patent ductus arteriosus: with summary of four surgically treated cases. Ann Surg 1939;110:321–356. 2. Wolff GS, Rowland TW, Ellison RC. Surgically induced right bundle-branch block with left anterior hemiblock: an ominous sign in postoperative tetralogy of Fallot. Circulation 1972;46:587–594. 3. Warnes CA, Liberthson R, Danielson GK, Dore A, Harris L, Hoffman JI, Somerville J, Williams RG, Webb GD. Task force 1: the changing profile of congenital heart disease in adult life. J Am Coll Cardiol 2001;37:1170–1175. 4. Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of death in adults with congenital heart disease. Am J Cardiol 2000;86:1111–1116. 5. Nieminen HP, Jokinen EV, Sairanen HI. Causes of late deaths after pediatric cardiac surgery: a population-based study. J Am Coll Cardiol 2007;50:1263–1271. 6. Verheugt CL, Uiterwaal CS, van der Velde ET, Meijboom FJ, Pieper PG, van Dijk AP, Vliegen HW, Grobbee DE, Mulder BJ. Mortality in adult congenital heart disease. Eur Heart J 2010;31:1220–1229. 7. Silka MJ, Hardy BG, Menashe VD, Morris CD. A population-based prospective evaluation of risk of sudden cardiac death after operation for common congenital heart defects. J Am Coll Cardiol 1998;32:245–251. 8. Koyak Z, Harris L, de Groot JR, Silversides CK, Oechslin EN, Bouma BJ, Budts W, Zwinderman AH, Van Gelder IC, Mulder BJ. Sudden cardiac death in adult congenital heart disease. Circulation 2012;126:1944–1954. 9. Gallego P, Gonzalez AE, Sanchez-Recalde A, Peinado R, Polo L, Gomez-Rubin C, Lopez-Sendon JL, Oliver JM. Incidence and predictors of sudden cardiac arrest in adults with congenital heart defects repaired before adult life. Am J Cardiol 2012;110:109–117. 10. Gillette PC, Yeoman MA, Mullins CE, McNamara DG. Sudden death after repair of tetralogy of Fallot: electrocardiographic and electrophysiologic abnormalities. Circulation 1977;56:566–571. 11. Zeppenfeld K, Schalij MJ, Bartelings MM, Tedrow UB, Koplan BA, Soejima K, Stevenson WG. Catheter ablation of ventricular tachycardia after repair of congenital heart disease: electroanatomic identification of the critical right ventricular isthmus. Circulation 2007;116:2241–2252. 12. Kriebel T, Saul JP, Schneider H, Sigler M, Paul T. Noncontact mapping and radiofrequency catheter ablation of fast and hemodynamically unstable ventricular tachycardia after surgical repair of tetralogy of Fallot. J Am Coll Cardiol 2007;50:2162–2168. 13. Sherwin ED, Triedman JK, Walsh EP. Update on interventional electrophysiology in patients with congenital heart disease: evolving solutions for complex hearts. Circ Arrhythm Electrophysiol 2013;6:1032–1040.

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