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Arrhythmias in a long-term adult survivor with uncorrected tetralogy of Fallot: Case report and review of the literature☆ Colin S. Hirst, MD, a Saadeh Jureidini, MD, b Paul J. Hauptman, MD a, c,⁎ a b

Department of Medicine, Saint Louis University School of Medicine, St. Louis, MO Department of Pediatrics, Saint Louis University School of Medicine, St. Louis, MO c Division of Cardiology, Saint Louis University School of Medicine, St. Louis, MO


We present a case of a middle-aged adult with uncorrected Tetralogy of Fallot (TOF) with pulmonary atresia who developed symptomatic supraventricular and ventricular arrhythmias. The lack of data regarding management of electrical and other complications in adults with uncorrected TOF is highlighted and emphasizes the need for a registry to better understand the medical management of long-standing adult survivors. © 2015 Elsevier Inc. All rights reserved.


Tetralogy of Fallot; Arrhythmias

Introduction Tetralogy of Fallot (TOF) remains the most common complex congenital heart defect. Properly timed surgical interventions have dramatically improved survival rates. The medical and surgical complications in patients with the typical form of TOF have been well described [1–3]. The smaller cohort of patients with uncorrected TOF with pulmonary atresia and origin of the pulmonary vessels from the aorta is less well characterized. This is in part because of the limited survival without palliative or complete hemodynamic correction. Several anatomic subgroups are particularly at risk for early death [4–6]. We present a case of a long-term adult survivor with uncorrected TOF with pulmonary atresia who developed both supraventricular and ventricular arrhythmias.

Case presentation A 52-year old male with uncorrected TOF and a failed attempt at surgical correction via sternotomy at 10 years of age presented with shortness of breath and recurrent palpitations. Fig. 1 provides a summary of the patient’s significant inpatient hospitalizations and outpatient surveillance with corresponding medical interventions prior to his emergency department presentation. His most recent anatomic evaluation occurred ten years prior when a contrast ☆

Disclaimers, Disclosures, Conflicts of Interest: None. ⁎ Corresponding author at: Saint Louis University Hospital, 3635 Vista Avenue, Saint Louis MO 63110, USA. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.04.006 0022-0736/© 2015 Elsevier Inc. All rights reserved.

enhanced computed tomography (CT) scan revealed lack of a main pulmonary artery and the presence of three major aortopulmonary collateral arteries (MAPCAs): at the level of the carina to the left lung, at the subcarinal level to both lungs and off the thoracic aorta through a web-like stenosis to the right lung. At the time, no further surgical intervention was advised. The patient first developed palpitations five years prior to presentation when runs of paroxysmal atrial fibrillation (PAF) were noted on telemetry. Sotalol (80 mg twice daily) was administered as an inpatient but non-sustained monomorphic ventricular tachycardia (NSVT) was detected on telemetry, with normal QT interval, prompting discontinuation. Amiodarone (400 mg twice daily) was initiated with apparent suppression of PAF. In the setting of thyroid dysfunction (hypothyroidism) amiodarone was stopped. When PAF recurred, dronedarone (400 mg twice daily) was started; the patient reported no recurrence of palpitations for several years. One year prior to presentation, a surveillance Holter showed recurrent supraventricular tachycardia (SVT) up to 3 min in duration and NSVT of up to 12 s (Fig. 2). In response, dronedarone was discontinued and metoprolol succinate was started at a dose of 50 mg once daily. Although the patient tolerated the beta blocker, a follow-up Holter showed persistence of NSVT up to 20 beats and sustained episodes of SVT at a rate of 150 bpm—the longest episode lasting one hour in duration. Shortly thereafter, the patient re-presented to the emergency department with recurrent palpitations lasting up to 30 s and associated mild dizziness and visual disturbance. The patient had not undergone recent phlebotomy and did not display


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Fig. 1. Timeline of significant inpatient hospitalizations and outpatient surveillance.

symptoms consistent with hyperviscosity syndrome. At the time of evaluation, his blood pressure was 130/60 mmHg and heart rate was 75 beats per minute. No apparent jugular venous distention or carotid bruits were noted. His lungs were clear to auscultation bilaterally without rales or wheezes. Cardiac auscultation was notable for a regular S1 and single S2 with a diastolic murmur noted at the left lower sternal border. Marked digital clubbing and cyanosis were apparent. Chest radiography revealed cardiomegaly with a right-sided aortic arch; lung fields were clear. Laboratories were notable for potassium of 4.5 mEq/L, magnesium of 2.5 mEq/L, creatinine of 1.4 mg/dL, hemoglobin of 23.4 g/dL and hematocrit of 69.8%. The initial 12-lead ECG showed sinus rhythm with a premature supra ventricular complex, left atrial enlargement, left anterior fascicular block with QRS complex widening and repolarization abnormality (Fig. 3). Echocardiographic evaluation revealed right ventricular hypertrophy with normal right ventricular global systolic function. An overriding aorta and a large, nonrestrictive membranous ventricular septal defect

were present. Left ventricular function was globally normal without regional wall motion abnormalities. The left ventricular ejection fraction was measured at 65%. Inpatient telemetry revealed NSVT up to 15 beats and self-terminating runs up to 30 s duration of SVT during which time the patient was symptomatic with palpitations ( Fig. 4). Given the relative stability achieved on dronedarone, the decision was made to restart this drug and increase his metoprolol dose. Other options, including formal electrophysiologic study with attempt at both SVT and VT ablation and implantable cardioverter defibrillator placement, were discussed with the patient and spouse, both of whom requested a conservative approach. Over a subsequent period of 18 months, the patient has not required re-hospitalization or phlebotomy. His exercise tolerance has deteriorated slightly but he remains engaged in family affairs and is able to carry out basic ADLs. He has not experienced pre-syncope and notes symptomatic palpitations of limited duration 1–2 times per month. He has refused consideration of heart–lung transplant.

Fig. 2. Outpatient surveillance capturing supraventricular tachycardia (A) and non-sustained monomorphic ventricular tachycardia (B), respectively.The tracings were recorded on Holter monitor in 2012. Patient noted palpitations at onset of each while at rest and while performing his activities of daily living.

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Fig. 3. Initial 12-lead ECG upon Emergency Department presentation.ECG reveals sinus rhythm with a premature supraventricular complex, left atrial enlargement, left anterior fascicular block with QRS widening and repolarization abnormality.

Discussion We present a case of an adult with uncorrected TOF and pulmonary atresia who developed electrical complications late in the fifth decade of life. The patient previously underwent an attempt at repair as a child via sternotomy but no pulmonary artery was identified and subsequent radiographic studies confirmed the presence of MAPCAs without intrapericardial pulmonary vessels. We believe that his unusual longevity is owed to a well-balanced intracardiac shunt and pulmonary circulation with three collaterals that permitted viable arterial saturations but with enough restriction to avoid overcirculation. This balance allowed for his survival into the sixth decade of life.

The natural history of this condition has been previously described and carries a high mortality rate [4–6]. Surgical intervention is designed to improve pulmonary blood flow and recruit the true pulmonary vascular bed through initial palliation followed by staged unifocalization of the MAPCAs [7,8]. The presence of MAPCAs portends a poor post-surgical prognosis [9], but a subset of patients with TOF with intrapericardial pulmonary arteries experiences favorable surgical outcomes despite systemic-to-pulmonary blood supply. Recent data with short-term follow-up suggest that native pulmonary artery morphology (intrapericardial versus intrapulmonary) is not a significant determinant of mortality after definitive surgical repair [10]. Survival without surgical correction is exceedingly rare but previously observed [11].

Fig. 4. Inpatient Hospital Telemetry.Non-sustained ventricular tachycardia recorded during inpatient 24-hour telemetry monitoring.


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Table 1 Summary of non-invasive diagnostic techniques utilized in the surveillance of ventricular arrhythmia in adult patients with uncorrected TOF. Diagnostic Technique

Year of Publication

Number of Patients


12-lead ECG SA-ECG

– 2006

– 33










– 1984

– 20





– – 2014

– – 30

No data Positive SA-ECG results found in 10% of unoperated adults with RV overload [21]. Ventricular arrhythmia ≥ Lown grade 2 in 58% and non-sustained ventricular tachycardia in 21% prior to surgical correction during 48-h Holter [13]. Ventricular arrhythmia ≥ Lown grade 2 recorded in 45% prior to surgical correction during 24-h Holter. Ventricular arrhythmia persistence rate of 85% was reported post-operatively [14]. Ventricular arrhythmia recorded in 31% prior to surgical correction [3]. Ventricular arrhythmia ≥ Lown grade 2 in 40% prior to surgical correction during 24-h Holter; ventricular arrhythmia incidence correlated with increasing age [16]. No data Intraoperative RVOT specimens from patients with TOF revealed increased fibrosis correlated with increasing age [18]. Intraoperative RV specimens from patients with TOF revealed trend of cellular changes of hypertrophy associated with increasing age [19]. Intraoperative RVOT specimens from patients with TOF revealed increased interstitial fibrosis, which correlated with advanced age, arterial desaturation and increased RV end diastolic pressure [16]. No data No data Increased late gadolinium enhancement [17].

T-wave alternans Histology

HR variability Electrophysiologic study Cardiac MRI

It has been hypothesized that well balanced pulmonary blood flow through systemic-to-pulmonary collaterals may be a key to symptom development beyond infancy [5] and rare patient longevity [12]. This observation adds uncertainty to the decision whether to proceed with electively planned surgical intervention in patients with presentation beyond infancy and without pronounced symptoms or signs of clinical instability. The long-term survival observed in our patient highlights this dilemma. Some complications observed in long standing uncorrected TOF appear to parallel those described in a generic population of patients with long standing cyanotic heart disease and Eisenmenger physiology, such as thromboembolism, hyperviscosity syndrome, hemoptysis and bleeding. Coronary artery disease has also been noted, presumably a reflection of long standing survival. Electrical complications of uncorrected TOF are particularly problematic. In patients with uncorrected TOF, ventricular arrhythmia incidence increases with age [13,14]. For example, Deanfield et al. noted an age-based increase in the incidence of ventricular arrhythmias: 58% of patients aged 16 years of age or older experienced some form of arrhythmia compared with a younger cohort aged 8 years or less [13]. Histopathologic studies report intraoperative findings of right ventricular myocardial fibrosis in patients undergoing late surgical correction. In fact, late repair, cyanosis and elevated right ventricular end-diastolic pressures were associated with pathologic histologic findings, suggesting that the exposure to sustained, elevated pressure of the right ventricle leads to

eventual mechanical–electrical uncoupling [15,16]. Data from cardiac MRI have shown increased right ventricular fibrosis in patients with Eisenmenger syndrome, linking a state of chronic hypoxemia to increased deposition of myocardial fibrosis [17]. Intraoperative surgical specimens from the right ventricle reveal defects of microscopic cellular disarray and macroscopic fibrosis [18,19]. Taken together, these observations couple hemodynamic and anatomic derangements that may provide the substrate for increased incidence of ventricular arrhythmia in late uncorrected survivors. In contrast, there are considerable data regarding the development of ventricular arrhythmias in patients who have had definitive repair [2,14]. Further, there are no known treatment algorithms or formal recommendations for arrhythmia screening (e.g. with Holter or other ambulatory monitoring) or management. This is likely based on the fact that unlike the surgically corrected population, in which non-invasive prognostic factors like QRS duration ≥ 180 ms or a rapid increase in QRS duration, a history of sustained ventricular tachycardia, a history of right ventriculotomy or severe left ventricular dysfunction portend an increased risk of SCD [20], little is known about the value of screening in the surgically uncorrected group (Table 1). The most consistent data are derived from pre-operative Holter monitoring prior to late surgical correction. Greater than 30% of adult patients with TOF undergoing late repair had significant ventricular arrhythmia prior to repair [3,13,14,16]. Perloff et al. have investigated the use of signal averaged ECG in adults with surgically uncorrected abnormalities, including, but not limited

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to, TOF [21]; in the entire group, 10% had abnormal findings. The significance and prognostic value of this isolated finding are unclear. We opted to use a number of pharmacologic agents (dronedarone, amiodarone, metoprolol) by extrapolating data from clinical trials that, in general, exclude patients with complex congenital heart disease. More aggressive approaches, such as electrophysiologic study with ablation, implantation of a cardioverter defibrillator (with transvenous or epicardial leads) and late surgical repair have been weighed against the peri-procedural risk. Data are sparse, but in one study ICD procedure complication rates were low [22]. Conversely, older age at the time of complete surgical repair is a risk factor for mortality. Additionally, although Hu et al. reported a 3% operative mortality rate among 30 patients between 40 and 60 years of age who underwent complete surgical repair, the mortality rate during a mean follow-up period of 9 years approached 30% [23]. A more recent study reported an in-hospital mortality rate of 16% in 19 adult patients undergoing late correction [3]. Given the stated patient preference and the fact that relative clinical stability was achieved, we opted to continue with a conservative approach. Nevertheless, the uncertainty about best practice in this setting suggests that a registry for patients with uncorrected TOF could help provide greater insight into management. Precedence for this proposal exists as exemplified by an international multicenter registry of patients with repaired TOF, which was designed to provide insight into the therapeutic strategies associated with improved late clinical outcomes [24]. References [1] Apitz C, Webb GD, Redington AN. Tetralogy of Fallot. Lancet 2009;374(9699):1462–71. [2] Gatzoulis MA, Till JA, Somerville J, Redington AN. Mechanoelectrical interaction in tetralogy of Fallot: QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death. Circulation 1995;92(2):231–7. [3] Dittrich S, Vogel M, Dahnert I, Berger F, Alexi-Meskihvili V, Lange PE. Surgical repair of tetralogy of Fallot in adults today. Clin Cardiol 1999;22(7):460–4. [4] Bertranou EG, Blackstone EH, Hazelrig JB, Turner ME, Kirklin JW. Life expectancy without surgery in tetralogy of Fallot. Am J Cardiol 1978;42(3):458–66. [5] Bull K, Somerville J, Ty E, Spiegelhalter D. Presentation and attrition in complex pulmonary atresia. J Am Coll Cardiol 1995;25(2):491–9. [6] Leonard H, Derrick G, O’Sullivan J, Wren C. Natural and unnatural history of pulmonary atresia. Heart 2000;84:499–503. [7] Iyer KS, Mee RB. Staged repair of pulmonary atresia with ventricular septal defect and major systemic to pulmonary artery collaterals. Ann Thorac Surg 1991;51(1):65–72. [8] Rome JJ, Mayer JE, Castaneda AR, Lock JE. Tetralogy of Fallot with pulmonary atresia. Rehabilitation of diminutive pulmonary arteries. Circulation 1993;88(4):1691–8.


[9] Amark KM, Karamlou T, O’Carroll A, MacDonald C, Freedom RM, Yoo SJ, et al. Independent factors associated with mortality, reintervention, and achievement of complete repair in children with pulmonary atresia with ventricular septal defect. J Am Coll Cardiol 2006;47(7):1448–56. [10] Davies B, Mussa S, Davies P, Stickley J, Jones TJ, Barron DJ, et al. Unifocalization of major aortopulmonary collateral arteries in pulmonary atresia with ventricular septal defect is essential to achieve excellent outcomes irrespective of native pulmonary artery morphology. J Thorac Cardiovasc Surg 2009;138(6):1269–75. [11] Fukui D, Kai H, Takeuchi T, Gondo T, Oba T, Mawatari K, et al. Longest survivor of pulmonary atresia with ventricular septal defect: welldeveloped major aortopulmonary collateral arteries demonstrated by multidetector computed tomography. Circulation 2011;124(19):2155–7. [12] Marelli AJ, Perloff JK, Child JS, Laks H. Pulmonary atresia with ventricular septal defect in adults. Circulation 1994;89(1):243–51. [13] Deanfield JE, McKenna WJ, Presbitero P, England D, Graham GR, Hallidie-Smith K. Ventricular arrhythmia in unrepaired and repaired tetralogy of Fallot. Relation to age, timing of repair, and haemodynamic status. Br Heart J 1984;52(1):77–81. [14] Sullivan ID, Presbitero P, Gooch VM, et al. Is ventricular arrhythmia in repaired tetralogy of Fallot an effect of operation or a consequence of the course of the disease? A prospective study. Br Heart J 1987;58:40–4. [15] Jones M, Ferrans VJ. Myocardial degeneration in congenital heart disease. Comparison of morphologic findings in young and old patients with congenital heart disease associated with muscular obstruction to right ventricular outflow. Am J Cardiol 1977;39:1051–63. [16] Chowdhury UK, Sathia S, Ray R, Singh R, Pradeep KK, Venugopal P. Histopathology of the right ventricular outflow tract and its relationship to clinical outcomes and arrhythmias in patients with tetralogy of Fallot. J Thorac Cardiovasc Surg 2006;132:270–7. [17] Broberg CS, Prasad SK, Carr C, Babu-Narayan SV, Dimopoulos K, Gatzoulis MA. Myocardial fibrosis in Eisenmenger syndrome: a descriptive cohort study exploring associations of late gadolinium enhancement with clinical status and survival. J Cardiovasc Magn Reson 2014;16:32. [18] Kawai S, Okada R, Kitamura K, Suzuki A, Saito S. A morphometrical study of myocardial disarray associated with right ventricular outflow tract obstruction. Jpn Circ J 1984;48(5):445–56. [19] Kuruvilla S, Balakrishnan K, Parvathy U. Right ventricular myocardium in Fallot's tetralogy: a light microscopic, morphometric and ultrastructural study. Images Paediatr Cardiol 2004;6(4):1–30. [20] Gatzoulis M, Balaji S, Webber S, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet 2000;356:975–81. [21] Perloff JK, Middlekauf HR, Child JS, Stevenson WG, Miner PD, Goldberg GD. Usefulness of post-ventriculotomy signal averaged electrocardiograms in congenital heart disease. Am J Cardiol 2006;98(12):1646–51. [22] Khanna AD, Warnes CA, Phillips SD, Lin G, Brady PA. Singlecenter experience with implantable cardioverter-defibrillators in adults with complex congenital heart disease. Am J Cardiol 2011;108(5):729–34. [23] Hu DC, Seward JB, Puga FJ, Fuster V, Tajik AJ. Total correction of tetralogy of Fallot at age 40 years and older: long-term follow-up. J Am Coll Cardiol 1985;5:40–4. [24] Valente AM, Gauvreau K, Assenza GE, Babu-Narayan SV, Evans SP, Gatzoulis M, et al. Rationale and design of an International Multicenter Registry of patients with repaired tetralogy of Fallot to define risk factors for late adverse outcomes: the INDICATOR cohort. Pediatr Cardiol 2013;34(1):95–104.

Arrhythmias in a long-term adult survivor with uncorrected tetralogy of Fallot: Case report and review of the literature.

We present a case of a middle-aged adult with uncorrected Tetralogy of Fallot (TOF) with pulmonary atresia who developed symptomatic supraventricular ...
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