Late arrhythmia in patients with repaired tetralogy of Fallot: who is at risk?

Open access


Tetralogy of Fallot (TOF) is the most common cause of cyanotic congenital heart defect. Over the last century, the life expectancy of TOF patients has significantly improved. This, however, has brought new challenges both to patients and their health-care providers, the main of them being late arrhythmia. Ironically, late arrhythmia is predominantly generated due to the fibrotic scars caused by the life-saving surgical repair. Once the first two mainly arrhythmia-free decades after the repair pass, the risk of developing late arrhythmia and, therefore, SCD becomes substantial. Consequently, young adults with repaired Tetralogy of Fallot (rTOF) require careful outpatient monitoring.

There have been many attempts to predict the risk of life-threatening arrhythmia in rTOF patients. This has led to the defining of various risk factors, ranging from the widely used QRS prolongation to novel predictors, derived from cardiac magnetic resonance (CMR) based anatomical findings (left ventricular dyssynchrony indexes, right ventricular output tract akinetic length, right ventricular mass-to-volume ratio). The latter predictors have recently established CMR as a tool of high significance in evaluation of rTOF patients.

Although the role of Holter monitoring findings in rTOF patient-assessment remains unclear, it may be useful in those who are 25 years and older. Implantable cardioverter–defibrillator (ICD) implantation is the first-line treatment for secondary prevention of sudden cardiac death (SCD). rTOF patients suffer from the highest rate of inappropriate and the lowest rate of appropriate ICD shocks, when compared to other congenital heart diseases. As a consequence, ICD implantation for primary SCD prevention should be carefully weighed. Catheter-based ablation therapy leads to high rate of initial success when abolishing monomorphic ventricular tachycardia and intra-atrial reentrant tachycardia, however recurrence rates remain high.

[1] Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002;39:1890–900.

[2] Bacha EA, Scheule AM, Zurakowski D, Erickson LC, Hung J, Lang P, et al. Long-term results after early primary repair of tetralogy of Fallot. J Thorac Cardiovasc Surg 2001;122:154–61.

[3] Parry AJ, McElhinney DB, Kung GC, Reddy VM, Brook MM, Hanley FL. Elective primary repair of acyanotic tetralogy of Fallot in early infancy: overall outcome and impact on the pulmonary valve. J Am Coll Cardiol 2000;36:2279–83.

[4] Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD, Ilstrup DM, et al. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med 1993;329:593–9.

[5] Chiu S-N, Wang J-K, Chen H-C, Lin M-T, Wu E-T, Chen C-A, et al. Long-term survival and unnatural deaths of patients with repaired tetralogy of Fallot in an Asian cohort. Circ Cardiovasc Qual Outcomes 2012;5:120–5.

[6] Nollert G, Fischlein T, Bouterwek S, Böhmer C, Klinner W, Reichart B. Long-term survival in patients with repair of tetralogy of Fallot: 36-year follow-up of 490 survivors of the first year after surgical repair. J Am Coll Cardiol 1997;30:1374–83.

[7] Nieminen HP, Jokinen EV, Sairanen HI. Causes of late deaths after pediatric cardiac surgery: a population-based study. J Am Coll Cardiol 2007;50:1263–71.

[8] Garson A Jr, Randall DC, Gillette PC, Smith RT, Moak JP, McVey P, et al. Prevention of sudden death after repair of tetralogy of Fallot: Treatment of ventricular arrhythmias. J Am Coll Cardiol 1985;6:221–7.

[9] Khairy P, Aboulhosn J, Gurvitz MZ, Opotowsky AR, Mongeon F-P, Kay J, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010;122:868–75.

[10] Gatzoulis MA, Balaji S, Webber S, Siu S, Hokanson J, Poile C, 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.

[11] Harrison DA, Harris L, Siu SC, MacLoghlin CJ, Connelly MS, Webb GD, et al. Sustained ventricular tachycardia in adult patients late after repair of tetralogy of Fallot. J Am Coll Cardiol 1997;30:1368–73.

[12] Misaki T, Tsubota M, Watanabe G, Watanabe Y, Matumoto Y, Ishida K, et al. Surgical treatment of ventricular tachycardia after surgical repair of tetralogy of Fallot. Relation between intraoperative mapping and histological findings. Circulation 1994;90:264–71.

[13] Dietl CA, Cazzaniga ME, Dubner SJ, Pérez-Baliño NA, Torres AR, Favaloro RG. Life-threatening arrhythmias and RV dysfunction after surgical repair of tetralogy of Fallot. Comparison between transventricular and transatrial approaches. Circulation 1994;90:II7–12.

[14] Therrien J, Siu SC, Harris L, Dore A, Niwa K, Janousek J, et al. Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot. Circulation 2001;103:2489–94.

[15] Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of death in adults with congenital heart disease. Am J Cardiol 2000;86:1111–6.

[16] James FW, Kaplan S, Chou TC. Unexpected cardiac arrest in patients after surgical correction of tetralogy of Fallot. Circulation 1975;52:691–5.

[17] Gillette PC, Yeoman MA, Mullins CE, McNamara DG. Sudden death after repair of tetralogy of Fallot. Electrocardiographic and electrophysiologic abnormalities. Circulation 1977;56:566–71.

[18] Koyak Z, Harris L, de Groot JR, Silversides CK, Oechslin EN, Bouma BJ, et al. Sudden cardiac death in adult congenital heart disease. Circulation 2012;126:1944–54.

[19] Kremers MS, Wells PJ, Black WH, Solodyna MA. Entrainment of ventricular tachycardia in postoperative tetralogy of Fallot. Pacing Clin Electrophysiol 1988;11:1310–4.

[20] Horowitz LN, Vetter VL, Harken AH, Josephson ME. Electrophysiologic characteristics of sustained ventricular tachycardia occurring after repair of tetralogy of Fallot. Am J Cardiol 1980;46:446–52.

[21] Kugler JD, Pinsky WW, Cheatham JP, Hofschire PJ, Mooring PK, Fleming WH. Sustained ventricular tachycardia after repair of tetralogy of Fallot: New electrophysiologic findings. Am J Cardiol 1983;51:1137–43.

[22] Downar E, Harris L, Kimber S, Mickleborough L, Williams W, Sevaptsidis E, et al. Ventricular tachycardia after surgical repair of tetralogy of Fallot: results of intraoperative mapping studies. J Am Coll Cardiol 1992;20:648–55.

[23] Khairy P, Landzberg MJ, Gatzoulis MA, Lucron H, Lambert J, Marçon F, et al. Value of programmed ventricular stimulation after tetralogy of Fallot repair: a multicenter study. Circulation 2004;109:1994–2000.

[24] Khairy P. Programmed ventricular stimulation for risk stratification in patients with tetralogy of Fallot: a Bayesian perspective. Nat Clin Pract Cardiovasc Med 2007;4:292–3.

[25] Roos-Hesselink J, Perlroth MG, McGhie J, Spitaels S. Atrial arrhythmias in adults after repair of tetralogy of Fallot: Correlations with clinical, exercise, and echocardiographic findings. Circulation 1995;91:2214–9.

[26] Valente AM, Gauvreau K, Assenza GE, Babu-Narayan SV, Schreier J, Gatzoulis MA, et al. Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort. Heart 2014;100:247–53.

[27] Rosianu S, Paprika D, Osztheimer I, Temesvari A, Szili-Torok T. Echocardiographic evaluation of patients with undocumented arrhythmias occurring in adults late after repair of tetralogy of Fallot. Eur J Echocardiogr 2009;10:139–43.

[28] Karl TR, Sano S, Pornviliwan S, Mee RB. Tetralogy of Fallot: favorable outcome of nonneonatal transatrial, transpulmonary repair. Ann Thorac Surg 1992;54:903–7.

[29] Al Habib HF, Jacobs JP, Mavroudis C, Tchervenkov CI, O’Brien SM, Mohammadi S, et al. Contemporary patterns of management of tetralogy of Fallot: data from the Society of Thoracic Surgeons Database. Ann Thorac Surg 2010;90:813–20.

[30] Kim H, Sung SC, Kim SH, Chang YH, Lee HD, Park JA, et al. Early and late outcomes of total repair of tetralogy of Fallot: risk factors for late right ventricular dilatation. Interact Cardiovasc Thorac Surg 2013;17:956–62.

[31] Reddy VM, Liddicoat JR, McElhinney DB, Brook MM, Stanger P, Hanley FL. Routine primary repair of tetralogy of Fallot in neonates and infants less than three months of age. Ann Thorac Surg 1995;60:S592–6.

[32] Stellin G, Milanesi O, Rubino M, Michielon G, Bianco R, Moreolo GS, et al. Repair of tetralogy of Fallot in the first six months of life: transatrial versus transventricular approach. Ann Thorac Surg 1995;60:S588–91.

[33] Fraser CD Jr, McKenzie ED, Cooley DA. Tetralogy of Fallot: surgical management individualized to the patient. Ann Thorac Surg 2001;71:1556–63.

[34] Stewart RD, Backer CL, Young L, Mavroudis C. Tetralogy of Fallot: results of a pulmonary valve-sparing strategy. Ann Thorac Surg 2005;80:1431–9.

[35] Niu MC, Morris SA, Morales DL, Fraser CD Jr, Kim JJ. Low incidence of arrhythmias in the right ventricular infundibulum sparing approach to tetralogy of Fallot repair. Pediatr Cardiol 2014;35:261–9.

[36] Mahle WT, McBride MG, Paridon SM. Exercise performance in tetralogy of Fallot: the impact of primary complete repair in infancy. Pediatr Cardiol 2002;23:224–9.

[37] Tamesberger MI, Lechner E, Mair R, Hofer A, Sames-Dolzer E, Tulzer G. Early primary repair of tetralogy of Fallot in neonates and infants less than four months of age. Ann Thorac Surg 2008;86:1928–35.

[38] Vohra HA, Adamson L, Haw MP. Is early primary repair for correction of tetralogy of Fallot comparable to surgery after 6 months of age? Interact Cardiovasc Thorac Surg 2008;7:698–701.

[39] Gladman G, Mccrindle BW, Williams WG, Freedom RM, Benson LN. The modified Blalock-Taussig shunt: clinical impact and morbidity in Fallot’s tetralogy in the current era. J Thorac Cardiovasc Surg 1997;114:25–30.

[40] Oosterhof T, van Straten A, Vliegen HW, Meijboom FJ, van Dijk AP, Spijkerboer AM, et al. Preoperative thresholds for pulmonary valve replacement in patients with corrected tetralogy of Fallot using cardiovascular magnetic resonance. Circulation 2007;116:545–51.

[41] Abd El Rahman MY, Abdul-Khaliq H, Vogel M, Alexi-Meskishvili V, Gutberlet M, Lange PE. Relation between right ventricular enlargement, QRS duration, and right ventricular function in patients with tetralogy of Fallot and pulmonary regurgitation after surgical repair. Heart 2000;84:416–20.

[42] Rebergen SA, Chin JG, Ottenkamp J, van der Wall EE, de Roos A. Pulmonary regurgitation in the late postoperative follow-up of tetralogy of Fallot. Volumetric quantitation by nuclear magnetic resonance velocity mapping. Circulation 1993;88:2257–66.

[43] Meagher SO, Ganigara M, Tanous DJ, Celermajer DS, Puranik R. Progress of right ventricular dilatation in adults with repaired tetralogy of Fallot and free pulmonary regurgitation. Int J Cardiol Heart Vessels 2014;3:28–31.

[44] Therrien J, Provost Y, Merchant N, Williams W, Colman J, Webb G. Optimal timing for pulmonary valve replacement in adults after tetralogy of Fallot repair. Am J Cardiol 2005;95:779–82.

[45] Buechel ER, Dave HH, Kellenberger CJ, Dodge-Khatami A, Pretre R, Berger F, et al. Remodelling of the right ventricle after early pulmonary valve replacement in children with repaired tetralogy of Fallot: assessment by cardiovascular magnetic resonance. Eur Heart J 2005;26:2721–7.

[46] Geva T, Sandweiss BM, Gauvreau K, Lock JE, Powell AJ. Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. J Am Coll Cardiol 2004;43:1068–74.

[47] Wald RM, Redington AN, Pereira A, Provost YL, Paul NS, Oechslin EN, et al. Refining the assessment of pulmonary regurgitation in adults after tetralogy of Fallot repair: should we be measuring regurgitant fraction or regurgitant volume? Eur Heart J 2009;30:356–61.

[48] Mooij CF, de Wit CJ, Graham DA, Powell AJ, Geva T. Reproducibility of MRI measurements of right ventricular size and function in patients with normal and dilated ventricles. J Magn Reson Imaging 2008;28:67–73.

[49] Knauth AL, Gauvreau K, Powell AJ, Landzberg MJ, Walsh EP, Lock JE, et al. Ventricular size and function assessed by cardiac MRI predict major adverse clinical outcomes late after tetralogy of Fallot repair. Heart 2008;94:211–6.

[50] Van Huysduynen BH, van Straten A, Swenne CA, Maan AC, van Eck HJ, Schalij MJ, et al. Reduction of QRS duration after pulmonary valve replacement in adult Fallot patients is related to reduction of right ventricular volume. Eur Heart J 2005;26:928–32.

[51] Vliegen HW, van Straten A, de Roos A, Roest AA, Schoof PH, Zwinderman AH, et al. Magnetic resonance imaging to assess the hemodynamic effects of pulmonary valve replacement in adults late after repair of tetralogy of Fallot. Circulation 2002;106:1703–7.

[52] Van Straten A, Vliegen HW, Hazekamp MG, Bax JJ, Schoof PH, Ottenkamp J, et al. Right ventricular function after pulmonary valve replacement in patients with tetralogy of Fallot. Radiology 2004;233:824–9.

[53] Geva T, Gauvreau K, Powell AJ, Cecchin F, Rhodes J, Geva J, et al. Randomized trial of pulmonary valve replacement with and without right ventricular remodeling surgery. Circulation 2010;122:S201–8.

[54] Tzemos N, Harris L, Carasso S, Subira LD, Greutmann M, Provost Y, et al. Adverse left ventricular mechanics in adults with repaired tetralogy of Fallot. Am J Cardiol 2009;103:420–5.

[55] Horowitz LN, Simson MB, Spear JF, Josephson ME, Moore EN, Alexander JA, et al. The mechanism of apparent right bundle branch block after transatrial repair of tetralogy of Fallot. Circulation 1979;59:1241–52.

[56] Khairy P, Marelli AJ. Clinical use of electrocardiography in adults with congenital heart disease. Circulation 2007;116:2734–46.

[57] 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;92:231–7.

[58] Uebing A, Gibson DG, Babu-Narayan SV, Diller GP, Dimopoulos K, Goktekin O, et al. Right ventricular mechanics and QRS duration in patients with repaired tetralogy of Fallot: implications of infundibular disease. Circulation 2007;116:1532–9.

[59] Babu-Narayan SV, Kilner PJ, Li W, Moon JC, Goktekin O, Davlouros PA, et al. Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of Fallot and its relationship to adverse markers of clinical outcome. Circulation 2006;113:405–13.

[60] Dubin AM, Feinstein JA, Reddy VM, Hanley FL, Van Hare GF, Rosenthal DN. Electrical resynchronization: a novel therapy for the failing right ventricle. Circulation 2003;107:2287–9.

[61] Ghai A, Silversides C, Harris L, Webb GD, Siu SC, Therrien J. 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;40:1675–80.

[62] Ortega M, Triedman JK, Geva T, Harrild DM. Relation of left ventricular dyssynchrony measured by cardiac magnetic resonance tissue tracking in repaired tetralogy of Fallot to ventricular tachycardia and death. Am J Cardiol 2011;107:1535–40.

[63] Davlouros PA, Kilner PJ, Hornung TS, Li W, Francis JM, Moon JC, et al. Right ventricular function in adults with repaired tetralogy of Fallot assessed with cardiovascular magnetic resonance imaging: Detrimental role of right ventricular outflow aneurysms or akinesia and adverse right-to-left ventricular interaction. J Am Coll Cardiol 2002;40:2044–52.

[64] Bonello B, Kempny A, Uebing A, Li W, Kilner PJ, Diller GP, et al. Right atrial area and right ventricular outflow tract akinetic length predict sustained tachyarrhythmia in repaired tetralogy of Fallot. Int J Cardiol 2013;168:3280–6.

[65] Rodriguez FH, Moodie DS, Neeland M, Adams GJ, Snyder CS. Identifying arrhythmias in adults with congenital heart disease by 24-h ambulatory electrocardiography. Pediatr Cardiol 2012;33:591–5.

[66] Czosek RJ, Anderson J, Khoury PR, Knilans TK, Spar DS, Marino BS. Utility of ambulatory monitoring in patients with congenital heart disease. Am J Cardiol 2013;111:723–30.

[67] Khairy P, Van Hare GF, Balaji S, Berul CI, Cecchin F, Cohen MI, et al. PACES/HRS Expert Consensus Statement on the recognition and management of arrhythmias in adult congenital heart disease: Developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Heart Rhythm 2014;11:e102–65.

[68] Khairy P, Harris L, Landzberg MJ, Viswanathan S, Barlow A, Gatzoulis MA, et al. Implantable cardioverter-defibrillators in tetralogy of Fallot. Circulation 2008;117:363–70.

[69] Yap SC, Roos-Hesselink JW, Hoendermis ES, Budts W, Vliegen HW, Mulder BJ, et al. Outcome of implantable cardioverter defibrillators in adults with congenital heart disease: a multi-centre study. Eur Heart J 2007;28:1854–61.

[70] Dore A, Santagata P, Dubuc M, Ee L. Implantable cardioverter defibrillators in adults with congenital heart disease: A single center experience. Pacing Clin Electrophysiol 2004;27:47–51.

[71] Koyak Z, de Groot JR, Van Gelder IC, Bouma BJ, van Dessel PF, Budts W, et al. Implantable cardioverter defibrillator therapy in adults with congenital heart disease: who is at risk of shocks? Circ Arrhythm Electrophysiol 2012;5:101–10.

[72] Friedmann E, Thomas SA, Inguito P, Kao CW, Metcalf M, Kelley FJ, et al. Quality of life and psychological status of patients with implantable cardioverter defibrillators. J Interv Card Electrophysiol 2006;17:65–72.

[73] Witte KK, Pepper CB, Cowan JC, Thomson JD, English KM, Blackburn ME. Implantable cardioverter–defibrillator therapy in adult patients with tetralogy of Fallot. Europace 2008;10:926–30.

[74] Zeppenfeld K, Schalij MJ, Bartelings MM, Tedrow UB, Koplan BA, Soejima K, et al. Catheter ablation of ventricular tachycardia after repair of congenital heart disease: electroanatomic identification of the critical right ventricular isthmus. Circulation 2007;116:2241–52.

[75] Morwood JG, Triedman JK, Berul CI, Khairy P, Alexander ME, Cecchin F, et al. Radiofrequency catheter ablation of ventricular tachycardia in children and young adults with congenital heart disease. HeartRhythm 2004;1:301–8.

[76] 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;50:2162–8.

[77] Mah DY, Alexander ME, Cecchin F, Walsh EP, Triedman JK. The electroanatomic mechanisms of atrial tachycardia in patients with tetralogy of Fallot and double outlet right ventricle. J Cardiovasc Electrophysiol 2011;22:1013–7.

[78] Triedman JK, DeLucca JM, Alexander ME, Berul CI, Cecchin F, Walsh EP. Prospective trial of electroanatomically guided, irrigated catheter ablation of atrial tachycardia in patients with congenital heart disease. HeartRhythm 2005;2:700–5.

[79] Opic P, Yap SC, Van Kranenburg M, Van Dijk AP, Budts W, Vliegen HW, et al. Atrial-based pacing has no benefit over ventricular pacing in preventing atrial arrhythmias in adults with congenital heart disease. Europace 2013;15:1757–62.

[80] Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES, et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006;295:165–71.

Seminars in Cardiovascular Medicine

The Journal of Lithuanian Heart Association

Journal Information


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 518 329 20
PDF Downloads 178 138 9