This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gatzoulis, M. A. Articles by Redington, A. N. Search for Related Content PubMed PubMed Citation Articles by Gatzoulis, M. A. Articles by Redington, A. N.

(Circulation. 1995;92:231-237.)
© 1995 American Heart Association, Inc.

Articles

Mechanoelectrical Interaction in Tetralogy of Fallot

QRS Prolongation Relates to Right Ventricular Size and Predicts Malignant Ventricular Arrhythmias and Sudden Death

Michael A. Gatzoulis, MD; Jan A. Till, MD; Jane Somerville, MD, FRCP; Andrew N. Redington, MD, FRCP

From the Department of Paediatric Cardiology (M.A.G., J.A.T., A.N.R.), Grown-up Congenital Heart Unit (J.S.), Royal Brompton Hospital and National Heart and Lung Institute, London, England.

Correspondence to Dr Andrew N. Redington, Department of Paediatric Cardiology, Royal Brompton Hospital/National Heart and Lung Institute, Sydney St, London, UK, SW3 6NP.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background Life-threatening ventricular arrhythmia and sudden death remain serious late complications after tetralogy of Fallot repair. Nevertheless, there remains no clear way of predicting which patients are at risk.

Methods and Results The study population included a total of 178 adult survivors (mean follow-up, 21.4 years) of tetralogy of Fallot repair who were currently attending our clinic. Mechanoelectrical relations were sought in 41 of the patients (mean follow-up, 23.6 years) who were operated on by one surgeon and who were prospectively studied with a 12-lead ECG, chest radiography, and two-dimensional and Doppler echocardiography. Nine patients (mean follow-up, 17 years) from the total group of 178 were identified as having had sustained ventricular tachycardia (8 with near-miss sudden death), and their ECGs, Holter monitor readings, electrophysiological studies, and chest radiographs were reviewed. The case notes of an additional 4 patients with postoperative sudden cardiac death also were available for review. QRS duration in the 41 patients in whom mechanoelectrical interaction was sought ranged between 90 and 200 milliseconds and correlated with cardiothoracic ratio (CTR) on chest radiography (r=.64, P<.001) and with right ventricular size on echocardiography (r=.43, P<.02). Twenty of the 41 patients had restrictive right ventricular Doppler physiology (reduced ventricular compliance) with mean QRS duration of 129.3±20 milliseconds and mean CTR of 0.51±0.03. The remaining 21 patients with no evidence of right ventricular restriction had prolonged QRS duration of 157.5±13.2 milliseconds (P<.001) and CTR of 0.55±0.04 (P<.04) compared with the restrictive. In the 9 patients with ventricular tachycardia, the QRS duration ranged from 180 to 230 milliseconds (mean, 198.9±17.6 milliseconds), and the CTR ranged from 0.54 to 0.9 (mean, 0.67±0.12) (P<.0001 and P<.01, respectively, compared with patients without life-threatening arrhythmias). All patients with documented sustained ventricular tachycardia and the 4 patients with sudden death had a QRS duration of 180 milliseconds (100% sensitivity).

Conclusions Chronic right ventricular volume overload after tetralogy of Fallot repair is related to diastolic function and correlates with QRS prolongation. The risk of symptomatic arrhythmia is high when marked right ventricular enlargement and QRS prolongation develop. A QRS duration on the resting ECG of 180 milliseconds is the most sensitive predictor of life-threatening ventricular arrhythmias yet described.

Key Words: tetralogy of Fallot • arrhythmia • death • sudden • ventricles

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Arrhythmias remain a cause of morbidity and mortality after repair of tetralogy of Fallot.^{1 2 3} Sudden death, attributed to sustained ventricular arrhythmias, occurs in as many as 6% of patients after tetralogy of Fallot repair.^{1 4} Current management strategies for these patients vary widely, ranging from treatment for symptomatic patients only⁵ to active treatment of ventricular premature beats in asymptomatic patients.⁶ However, in a recent report, the presence of asymptomatic "complex ventricular arrhythmia" on Holter monitoring did not predict a worse outcome.⁷ There is some evidence that the chance of sudden death is increased in patients with residual right ventricular systolic and diastolic dysfunction.^{8 9 10} There are compelling data to suggest that left ventricular electrical instability may result from mechanical events (primarily ventricular dilatation and stretch),^{11 12} although such information in humans has been derived in the setting of ischemia. Tetralogy of Fallot represents a potentially important model for mechanolectricalal interactions because it is a nonischemic dilated model with both intrinsic myocardial and artificial scarring. A rational approach to this common clinical problem requires identification of patients who are clearly at risk of sudden death. The purpose of the present study was to address this problem by searching for any mechanolectricalal relation in adult survivors after tetralogy of Fallot repair that might relate to symptomatic ventricular arrhythmias and sudden death.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
We first performed a detailed study of 41 patients who underwent total repair of tetralogy of Fallot between 1958 and 1979, with a minimum follow-up of 15 years. This subgroup was chosen from the total number of 178 adult survivors who were followed in our clinic because they represent one of the earliest British cohorts of patients undergoing repair and they were operated on by one surgeon who used a uniform approach (otherwise, they were completely unselected, other than the fact that they had survived). Their age at the time of the study ranged from 16 to 46 years (mean, 28.8 years), and their age at complete repair ranged from 9 months to 18 years (mean, 5.2 years). Five patients (12.2%) had previously undergone palliative surgery (Blalock-Taussig shunts in 3 and the Brock procedure in 2). During repair, access in the majority was via a combined right atriotomy and ventriculotomy, although in 7 patients the transatrial/pulmonary approach was used. All patients had extensive infundibular resection, 7 patients had a patch to the infundibulum, and only 1 patient required a transannular patch. Eight patients (19.5%) required repeat operation (residual ventricular septal defect closure in 3, repeat operation on the right ventricular outflow tract because of severe pulmonary stenosis/regurgitation in 3 and bacterial endocarditis in 1, and balloon valvuloplasty for pulmonary stenosis in 1).

The mechanoelectrical relation in these 41 patients was sought and then tested and applied in our group of 178 adult survivors of tetralogy of Fallot repair to establish whether this relation was sensitive, specific, or both. Two additional groups derived from the 178 patients currently attending our clinic were identified (Fig 1): a group of 9 patients with sustained ventricular tachycardia and a group of 11 patients with atrial flutter. Data were also available from hospital records on 4 cases of sudden death. Unfortunately, the case records of 6 patients who died suddenly before 1989 had been destroyed. These 178 patients represent a quaternary referral practice from different primary and specialist hospitals and with different surgeons; therefore, the observed incidence of hemodynamically important arrhythmias or sudden death in our patients may not be representative of an unselected cohort of patients after repair of tetralogy of Fallot. However, this does not influence the interpretation of our data.

View larger version (11K): [in this window] [in a new window]   Figure 1. Flow chart of the total number of patients studied, including subgroups. VT indicates ventricular tachycardia. See text for available records.

Techniques
Hemodynamic data were obtained for the 41 patients with detailed echocardiography as we have previously described.^{13 14} Right and left ventricular long-axis lengths were measured from two-dimensional echocardiograms in the four-chamber view at end diastole. Patients had a 12-lead surface resting ECG performed with a Hewlett-Packard PageWriter XLi (M1700A) at a speed of 25 mm/s and 1 mV/cm standardization and a posteroanterior chest radiograph. We identified that QRS width in these patients correlated to right ventricular size and related to both diastolic function and malignant arrhythmias. ECGs were then reviewed in the 178 patients (before drug therapy) and in the 4 cases of sudden death by two observers with no knowledge of the clinical, radiographic, or echocardiographic findings. Maximal QRS width in any lead was measured from the first to the last sharp vector crossing the isoelectric line. Data from all 16 patients who underwent electrophysiological study for symptoms (syncope or palpitations) also were reviewed. Ventricular stimulation was performed in all, as described by Wellens et al,¹⁵ including two extrastimuli at two or three sites at two rates. Rapid pacing was not performed. Standard conduction intervals were measured and AV conduction was analyzed with incremental atrial pacing.

Statistical Analysis
Group data are expressed as mean±SD. Student's t tests were used to compare normally distributed variables; otherwise, a Mann-Whitney U test was performed. Regression analysis was performed using the method of least squares. The null hypothesis was rejected when P<.05.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Mechanoelectrical Relation
Of the 41 patients studied in detail, 39 were in New York Heart Association functional class I (95.1%).

Biventricular Function
Twenty patients had evidence of right ventricular restrictive physiology (low right ventricular compliance), as demonstrated by the presence of antegrade diastolic flow in the pulmonary artery coinciding with atrial systole throughout the respiratory cycle. A detailed analysis of the patients' right ventricular diastolic function has been presented elsewhere.¹⁵ Biventricular systolic function was well preserved in all (left ventricular shortening fraction, 26% to 45%). Two patients had significant residual right ventricular outflow tract obstruction (>40 mm Hg). No attempt was made to measure the degree of pulmonary regurgitation because of the inherent inaccuracy of clinical and Doppler echocardiography methods in these patients.

ECG and Right Ventricular Size
All except 1 patient was in sinus rhythm, and all of the patients had a right bundle-branch block pattern on the surface ECG. It became apparent during the initial investigations that there was a clinically obvious difference in the QRS duration of the resting ECG of these patients. Maximum QRS duration ranged from 90 to 200 milliseconds and correlated with cardiothoracic ratio (CTR) on chest radiograph (r=.64, P<.001; Fig 2) and with right ventricular long-axis length when expressed as a ratio of right-to-left ventricle (r=.43, P<.02; Fig 3). Those with restrictive right ventricular Doppler physiology had a mean QRS duration of 129.3±20 milliseconds, significantly shorter than those without, who had a prolonged QRS duration (mean, 157.5±13 milliseconds; P<.001; Fig 4). The mean CTR was also smaller in those with restrictive physiology (0.51±0.03) compared with those without (0.55±0.04; P<.01). QRS duration was not particularly prolonged in the 2 patients with significant right ventricular outflow tract obstruction (150 ms/64 mm Hg and 130 ms/100 mm Hg, respectively).

View larger version (10K): [in this window] [in a new window]   Figure 2. Scatterplot of correlation between QRS duration and cardiothoracic ratio in the 41 patients studied in detail.

View larger version (8K): [in this window] [in a new window]   Figure 3. Plot of correlation between QRS duration and ratio of right to left ventricle (both are long axis length) in the 41 patients studied in detail. RV indicates right ventricle; LV, left ventricle.

View larger version (14K): [in this window] [in a new window]   Figure 4. Plot of QRS duration in the 41 patients in whom mechanolectricalal interactions were sought. The 2 patients with documented sustained ventricular tachycardia are indicated by squares. Restrictive indicates patients with restrictive Doppler right ventricular physiology; nonrestrictive, patients without Doppler evidence of restriction.

Sustained Ventricular Tachycardia
Nine patients (5%) of the 178 were identified as having had documented sustained ventricular tachycardia. Two of them were among the 41 patients in whom a mechanoelectrical relation was sought, both without evidence of restriction (QRS duration, 180 and 200 milliseconds, respectively). Eight of the 9 patients had syncopal episodes requiring cardiopulmonary resuscitation (near-miss sudden death). All 9 had undergone an electrophysiological study during which ventricular tachycardia was easily inducible with one or two extrastimuli and terminated, and a reentry mechanism was confirmed. The maximum QRS duration on the resting ECG before onset of sustained ventricular arrhythmia and before drug therapy ranged from 180 to 230 milliseconds (mean, 198.9±17.6 milliseconds), and CTR ranged from 0.54 to 0.9 (mean, 0.67±0.12), significantly longer (QRS, P<.0001) and larger (CTR, P<.01) compared with patients without life-threatening arrhythmias (Table).

View this table: [in this window] [in a new window]   Table 1. Clinical, ECG, and Radiological Details

Sudden Death
Four patients with sudden death after tetralogy of Fallot repair were identified from the available hospital records (age at repair: range, 0.5 to 29 years; mean, 8.9 years; and time from repair at death: range, 9 to 19 years; mean, 16 years). QRS duration on the ECG before death ranged from 180 to 220 milliseconds (mean, 193.8±18.9 milliseconds), and CTR ranged from 0.59 to 0.67 (mean, 0.63±0.03). As all patients were previously asymptomatic, they had not undergone electrophysiological studies. Their QRS duration combined with that of the syncopal arrhythmic patients from our complete group of 178 patients is compared with the QRS duration of the remainder of the patients studied (Fig 5).

View larger version (17K): [in this window] [in a new window]   Figure 5. Plot of QRS duration in 182 patients. Those with syncope and ventricular tachycardia (squares), sudden death (triangles), and the single syncopal patient with atrial flutter (star) are plotted separately.

Previous palliations, approach, age at repair or need for repeat operation, and age at follow-up were not significant factors in determining whether symptomatic ventricular tachycardia or sudden death occurred.

Atrial Flutter
Eleven patients (6.2%) with documented atrial flutter were identified from our total group of 178 survivors (age at repair: range, 6 to 21 years; mean, 10.4 years; and follow-up time: range, 16 to 30 years; mean, 23.3 years). The maximum QRS duration on the surface ECG ranged from 160 to 200 milliseconds (mean, 177.8±13 milliseconds), and CTR ranged from 0.57 to 0.78 (mean, 0.64±0.07). One patient, who had severe tricuspid regurgitation (CTR, 0.78; QRS, 200 milliseconds), was syncopal. The remaining 10 tolerated the arrhythmias well. There was no overlap of patients between the group with atrial flutter and the group with sustained ventricular tachycardia.

Seven additional patients of the 178 underwent electrophysiological studies (because of undiagnosed symptoms), during which no inducible sustained ventricular tachycardia was found. Four of the 7 patients were syncopal: 3 with neurogenic syncope and 1 with epilepsy. The other 3 were nonsyncopal patients with atrial flutter.

The mean age at repair of patients with significant arrhythmias and their mean follow-up time with maximum QRS width and CTR at onset of arrhythmia are shown in the Table.

Sensitivity and Specificity of QRS 180 Milliseconds as a Risk Marker of Malignant Ventricular Arrhythmias
There was no patient with sustained ventricular tachycardia or sudden death with a QRS duration of <180 milliseconds (100% sensitivity).

There are 9 additional patients, none of whom gave a history of life-threatening events, with a QRS duration of 180 milliseconds. Six of them had atrial flutter, and 3 had no documented arrhythmia. Therefore, the specificity of QRS duration of 180 milliseconds as a single predictor of symptomatic ventricular tachycardia is 94.7%. The negative predictive value for life-threatening ventricular arrhythmias or sudden death with a QRS duration of <180 milliseconds was 100%.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The introduction of open heart repair of tetralogy of Fallot by Lillehei and colleagues in 1955¹⁶ has transformed the outcome of a condition in which fewer than one fourth of patients could be expected to survive past the first decade¹⁷ to one in which early corrective surgery can be performed with a mortality rate of <5%. Although the late outcome of these patients is favorable in reported series,^{1 10 18} sudden death remains a complication. Sudden death has occurred in almost every large series with long postoperative follow-up,^{1 19 20} and death after tetralogy of Fallot repair is the most common cause of sudden death in childhood.²¹

Both atrial and ventricular arrhythmias are recognized after repair of tetralogy of Fallot, but there is no clear-cut relation between atrial arrhythmia and sudden death. There is no doubt, however, that patients who develop sustained ventricular tachycardia are at risk of syncope and sudden death. There is good evidence from electrophysiological studies that sustained ventricular tachycardia, in this setting, results from reentry,²² which requires areas of slow conduction. Right bundle-branch block is very common and may be central, "myocardial," or both.^{23 24} Furthermore, fragmented electrograms, indicative of localized areas of slowed conduction, have been recorded from both the inflow²⁵ and the outflow tracts²⁶ and throughout the right ventricle.²⁷ Finally, the ventriculotomy scar,²⁸ ventricular septal defect,²⁵ and outflow patch²⁶ have each been implicated as areas of potential block within the reentry circuit. Although patients with sustained ventricular tachycardia are relatively uncommon, nonsustained ventricular arrhythmia ranging from ventricular premature beats to nonsustained ventricular tachycardia is seen in as many as 42% of patients after repair of tetralogy on 24-hour tape.¹⁹ The great majority of such patients are asymptomatic. It has been suggested that ventricular electrical extra activity is a marker for patients at risk for sustained ventricular tachycardia and sudden death. This has led to asymptomatic patients with more than 30 ventricular premature beats per hour being treated with antiarrhythmic drugs.⁶ The wisdom of this has to be questioned.²⁹ The relation between these nonsustained ventricular arrhythmias (which may result from a different mechanism) and sustained ventricular tachycardia is far from clear. Many studies have attempted to identify risk factors for sudden death by examining the relation between hemodynamic and electrophysiological variables and the frequent ventricular ectopy seen on 24-hour tape recordings; results have been unclear. Even if they are a reliable marker of patients susceptible to sustained ventricular tachycardia and therefore sudden death, the value of treatment to suppress a marker is a matter of debate.³⁰ Cullen et al⁷ recently showed that even the so-called high-grade ventricular arrhythmias on Holter monitoring do not appear to be predictive for sudden death on long-term follow-up.⁷

Previous studies have emphasized the possible additional influence of persisting right ventricular hypertension⁸ and pulmonary regurgitation³¹ on late sudden death, and this suggests that a mechanoelectrical interaction may exist in these patients, but the basis of this phenomenon has not been explored. In the present study, we performed detailed studies of right ventricular diastolic function in one of the earliest cohorts of survivors of complete correction of tetralogy of Fallot. At a mean follow-up of 23.6 years, approximately half of the patients had evidence of restrictive right ventricular diastolic function. The presence of antegrade diastolic pulmonary arterial flow, which limits the degree of pulmonary regurgitation, is indicative of a limited end-diastolic volume.^{13 14} As a result, these patients have a significantly lower CTR, which in turn reflects lower right ventricular long-axis dimensions. The ultrastructural nature of the myocardial process that prevents progressive right ventricular dilatation, even in the presence of potentially free pulmonary regurgitation, is unknown but appears to be unrelated to surgical technique and other anthropometric details. Regardless of the cause, patients with restrictive right ventricular physiology have a significantly shorter QRS duration. Furthermore, we have shown a statistically significant correlation between right ventricular size and QRS duration for the group as a whole. Conversely, QRS width was not particularly prolonged in cases of significant residual right ventricular outflow obstruction alone, suggesting that the QRS prolongation reflects right ventricular dilation rather than an increase in right ventricular mass due to hypertrophy. That is, as the postoperative tetralogy right ventricle dilates, the QRS duration is prolonged, and this in turn creates the conditions required for reentry.

In the present study, all 9 patients with documented sustained ventricular tachycardia had a reentry mechanism confirmed during electrophysiological study. All had delayed conduction with a prolonged QRS complex of 180 milliseconds (mean, 200 milliseconds; P<.001 compared with nonarrhythmic patients) before the onset of tachycardia. It has been suggested that in the presence of large areas of delayed conduction, ventricular tachycardia is more likely to break down to ventricular fibrillation,³² and 8 of the 9 patients had experienced near-miss sudden death. Not surprisingly, the CTR was significantly larger in this subgroup compared with the nonsymptomatic arrhythmia patients.

Eleven of the patients (5%) had documented atrial flutter. Only 1 was syncopal, and this patient had a QRS width of 200 milliseconds at the onset of symptomatic arrhythmia. This patient has severe tricuspid regurgitation with gross cardiomegaly (CTR, 0.78). The mechanism of syncope in this case is uncertain, and we cannot exclude ventricular tachycardia even in the presence of atrial flutter. QRS duration and CTR ratio were relatively increased in the atrial flutter group compared with the nonarrhythmia patients (Table). Tricuspid regurgitation on echocardiography was significant in 8 of these patients, and this might be the cause of concomitant right atrial and right ventricular enlargement. These patients are clearly susceptible to atrial flutter and may, for the same reasons, also be predisposed to ventricular arrhythmias. Even so, a resting QRS duration of 180 milliseconds is a highly sensitive predictor of hemodynamically important arrhythmia in the group as a whole, with a negative predictive value of 100%.

We believe that the mechanical and electrical properties of the right ventricle after tetralogy of Fallot repair are interrelated, with a potentially causative relation between right ventricular dilation and life-threatening arrhythmias. Sustained ventricular tachycardias in this group are more common. We speculate that there is a subgroup of patients with both progressive dilatation of the right ventricle and a predisposition to ventricular arrhythmias. When a certain threshold of ventricular dilation and slowed conduction is reached (as demonstrated by a QRS duration of 180 milliseconds), these patients, who may be asymptomatic, are at risk of severe ventricular arrhythmia and sudden death. Zhou et al³³ showed stretch-induced ventricular arrhythmias in experimental models, whereas Waxman et al³⁴ showed that a decrease in right ventricular volume, caused by Valsalva's maneuver, can lead to termination of ventricular tachycardia in some patients. Exercise-induced sudden death in these patients may be related to transient further right ventricular dilatation secondary to increased stroke volume. Whether it follows that restoration of a competent right ventricular outflow tract by pulmonary valve replacement in cases of severe pulmonary incompetence with resultant marked right ventricular dilatation could alter the outcome remains speculative, however.

We have shown that the mechanical and electrical properties of the right ventricle after tetralogy of Fallot repair are interrelated. However, we recognize that our patients reflect the outcome of early surgery performed by many different surgeons, with different techniques. Furthermore, this is a retrospective, uncontrolled study with a potential for selection bias because of the nature of referrals. Nevertheless, it is reflective of these patients currently presenting in adult life.

It is not clear whether newer surgical strategies will influence outcome. The incidence of right bundle-branch block has been reduced by the transatrial approach to repair,²⁴ for example. The timing and nature of surgery also may affect the mechanolectricalal relation. Nevertheless, in our group of patients, those with restrictive right ventricular Doppler physiology are protected from the effects of pulmonary incompetence^{15 35} and late sustained ventricular arrhythmias.

The immediate clinical implications of our data are obvious. We now have a readily measurable, sensitive, and specific predictor for patients at risk of life-threatening ventricular arrhythmias late after repair of tetralogy of Fallot. Patients with a QRS duration of 180 milliseconds can be easily identified and evaluated. Their hemodynamic status should be examined. The use of electrophysiological study in this group may be able to further identify a subgroup of patients at risk of clinical sustained reentry ventricular tachycardia. This group may benefit from prophylactic antiarrhythmic therapy or more definitive treatment in the form of catheter ablation or surgery.

	Acknowledgments

 
We thank Dr S.Y. Ho for her help with the figures and diagrams.

Received October 26, 1994; revision received December 29, 1994; accepted January 10, 1995.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD, Ilstrup DM, McGoon DC, Kirklin JW, Danielson GK. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med. 1993;329:593-599. [Abstract/Free Full Text]
   
2. Rosing DR, Borer JS, Kent KM, Maron BJ, Seides SF, Morrow AG, Epstein SE. Long-term hemodynamic and electrocardiographic assessment following operative repair of tetralogy of Fallot. Circulation. 1978;58(suppl I):I-209-I-217.
   
3. Deanfield JE, McKenna WJ, Hallidie-Smith KA. Detection of late arrhythmia and conduction disturbance after correction of tetralogy of Fallot. Br Heart J. 1980;44:248-253. [Abstract/Free Full Text]
   
4. Garson A, Nihill MR, McNamara DG, Cooley DA. Status of the adult and adolescent after repair of tetralogy of Fallot. Circulation. 1979;59:1232-1240. [Free Full Text]
   
5. Garson A. Ventricular arrhythmias after repair of congenital heart disease: who needs treatment? Cardiol Young. 1991;1:177-181.
   
6. Garson A, Randall DG, Gillette PC, Smith RT, Moak JP, McVey P, McNamara DG. Prevention of sudden death after repair of tetralogy of Fallot: treatment of ventricular arrhythmias. J Am Coll Cardiol. 1985;6:221-227. [Abstract]
   
7. Cullen S, Celermajer DS, Franklin R, Deanfield JE. Prognostic significance of ventricular arrhythmia after repair of tetralogy of Fallot: a 12 year prospective study. J Am Coll Cardiol. 1994;23:1151-1155. [Abstract]
   
8. Marie PY, Marcon F, Brunotte F, Briancon S, Danchin N, Worms AM, Robert J, Pernot C. Right ventricular overload and induced sustained ventricular tachycardia in operatively `repaired' tetralogy of Fallot. Am J Cardiol. 1992;69:785-789. [Medline] [Order article via Infotrieve]
   
9. Wessel HU, Cunningham WJ, Paul MH, Bastanier CK, Muster AJ, Idriss FS. Exercise performance in tetralogy of Fallot after intracardiac repair. J Thorac Cardiovasc Surg. 1980;80:582-593. [Abstract]
   
10. Katz NM, Blackstone EH, Kirklin JW, Pacifico AD, Bargeron LM. Late survival and symptoms after repair of tetralogy of Fallot. Circulation. 1982;65:403-410. [Abstract/Free Full Text]
    
11. Hansen DE, Craig CS, Hondeghem LM. Stretch-induced arrhythmias in the isolated canine ventricle. Circulation. 1990;81:1094-1105. [Abstract/Free Full Text]
    
12. Dean JW, Lab MJ. Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology. Lancet. 1989;1:1309-1311. [Medline] [Order article via Infotrieve]
    
13. Redington AN, Penny D, Rigby ML, Hayes A. Antegrade diastolic pulmonary arterial flow as a marker of right ventricular restriction after complete repair of pulmonary atresia with intact septum and critical pulmonary valvar stenosis. Cardiol Young. 1992;2:382-386.
    
14. Gatzoulis MA, Clark AL, Cullen S, Newman CGH, Redington AN. Right ventricular diastolic function 15-35 years after repair of tetralogy of Fallot: restrictive physiology predicts superior exercise performance. Circulation. 1995;91:1775-1781. [Abstract/Free Full Text]
    
15. Wellens HJJ, Brugada P, Stevenson WG. Programmed electrical stimulation of the heart in patients with life-threatening ventricular arrhythmias: what is the significance of induced arrhythmias and what is the correct stimulation protocol? Circulation. 1985;72:1-7. [Free Full Text]
    
16. Lillehei CW, Cohen M, Warden HE, Read RC, Aust JB, DeWall RA, Varco RL. Direct vision intracardiac surgical correction of the tetralogy of Fallot, pentalogy of Fallot, and pulmonary atresia defects: report of first ten cases. Ann Surg. 1955;142:418-445. [Medline] [Order article via Infotrieve]
    
17. Bertranou EG, Blackstone EH, Hazelrig JB, Turner ME, Kirklin JW. Life expectancy without surgery in tetralogy of Fallot. Am J Cardiol. 1978;42:458-466. [Medline] [Order article via Infotrieve]
    
18. Lillehei CW, Varco RL, Cohen M, Warden HE, Gott VL, DeWall RA, Patton C, Moller JH. The first open heart corrections of tetralogy of Fallot: a 26-31 year follow-up of 106 patients. Ann Surg. 1986;204:490-502. [Medline] [Order article via Infotrieve]
    
19. Kavey REW, Blackman MS, Sondheimer HM. Incidence and severity of chronic ventricular dysrhythmias after repair of tetralogy of Fallot. Am Heart J. 1982;103:342-350. [Medline] [Order article via Infotrieve]
    
20. Quattlebaum TG, Varghese PJ, Neill CA, Donahoo JS. Sudden death among postoperative patients with tetralogy of Fallot: a follow-up study of 243 patients for an average of 12 years. Circulation. 1976;54:289-293. [Abstract/Free Full Text]
    
21. Garson A, McNamara DG. Sudden death in a paediatric cardiology population: relationship to prior arrhythmias. J Am Coll Cardiol. 1985;5:134B-137B.
    
22. Kremers MS, Wells PJ, Black WH, Solodyna MA. Entrainment of ventricular tachycardia in postoperative tetralogy of Fallot. PACE Pacing Clin Electrophysiol. 1988;11:1310-1314. [Medline] [Order article via Infotrieve]
    
23. Garson A, Porter CJ, Gillette PC, McNamara DG. Induction of ventricular tachycardia during electrophysiologic study after repair of tetralogy of Fallot. J Am Coll Cardiol. 1983;1:1493-1502. [Abstract]
    
24. Gelband H, Waldo AL, Kaiser GA, Bowman FO, Malm JR, Hoffman BF. Etiology of right bundle branch block in patients undergoing total correction of tetralogy of Fallot. Circulation. 1971;44:1022-1033. [Abstract/Free Full Text]
    
25. 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;51:1137-1143. [Medline] [Order article via Infotrieve]
    
26. Donwar E, Harris L, Kimber S, Mickleborough L, Williams W, Sevaptsidis E, Masse S, Chen TC, Chan A, Genga A, Glanz A. Ventricular tachycardia after surgical repair of tetralogy of Fallot: results of intraoperative mapping studies. J Am Coll Cardiol. 1992;20:648-655. [Abstract]
    
27. Deanfield JE, McKenna W, Rowland E. Local abnormalities of right ventricular depolarization after repair of tetralogy of Fallot: a basis for ventricular arrhythmia. Am J Cardiol. 1985;55:522-525. [Medline] [Order article via Infotrieve]
    
28. 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;46:446-452. [Medline] [Order article via Infotrieve]
    
29. Hoffman BF, Dangman KH. The role of antiarrhythmic drugs in sudden cardiac death. J Am Coll Cardiol. 1986;8:104A-109A.
    
30. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-412. [Abstract]
    
31. Redington AN, Oldershaw PJ, Shinebourne EA, Rigby ML. A new technique for the assessment of pulmonary regurgitation and its application to the assessment of right ventricular function before and after repair of tetralogy of Fallot. Br Heart J. 1992;67:470-473. [Abstract/Free Full Text]
    
32. Cassidy DM, Vassallo JA, Miller JM, Josephson ME. Differences in endocardial electrophysiologic characteristics in coronary artery disease patients with ventricular tachycardia versus cardiac arrest. Circulation. 1985;72(suppl III):III-160. Abstract.
    
33. Zhou BY, Lab MJ, Horner SH, Murphy CF, Harrision FG. Are there different mechanisms for stretch-induced ventricular premature contraction and fibrillation? Br Heart J. 1994;71(suppl):9. Abstract.
    
34. Waxman MB, Wald RW, Finley JP, Bonet JF, Downar E, Sharma AD. Valsalva termination of ventricular tachycardia. Circulation. 1980;62:843-851. [Abstract/Free Full Text]
    
35. Carvalho JS, Shinebourne EA, Busst C, Rigby ML, Redington AN. Exercise capacity after complete repair of tetralogy of Fallot: deleterious effects of residual pulmonary regurgitation. Br Heart J. 1992;67:470-473.
    

This article has been cited by other articles:

				A. Frigiola, V. Tsang, C. Bull, L. Coats, S. Khambadkone, G. Derrick, B. Mist, F. Walker, C. van Doorn, P. Bonhoeffer, et al. Biventricular Response After Pulmonary Valve Replacement for Right Ventricular Outflow Tract Dysfunction: Is Age a Predictor of Outcome? Circulation, September 30, 2008; 118(14_suppl_1): S182 - S190. [Abstract] [Full Text] [PDF]

				S. Rosianu, D. Paprika, I. Osztheimer, A. Temesvari, and T. Szili-Torok Echocardiographic evaluation of patients with undocumented arrhythmias occurring in adults late after repair of tetralogy of Fallot Eur J Echocardiogr, July 8, 2008; (2008) jen199v1. [Abstract] [Full Text] [PDF]

				P. Bordachar, X. Iriart, J. Chabaneix, F. Sacher, S. Lafitte, P. Jais, M. Haissaguerre, J. Clementy, P. Dos Santos, and J.-B. Thambo Presence of ventricular dyssynchrony and haemodynamic impact of right ventricular pacing in adults with repaired Tetralogy of Fallot and right bundle branch block Europace, July 4, 2008; (2008) eun178v1. [Abstract] [Full Text] [PDF]

				G. J.F. Hoohenkerk, P. H. Schoof, E. F. Bruggemans, M. Rijlaarsdam, and M. G. Hazekamp 28 years' experience with transatrial-transpulmonary repair of atrioventricular septal defect with tetralogy of fallot. Ann. Thorac. Surg., May 1, 2008; 85(5): 1686 - 1689. [Abstract] [Full Text] [PDF]

				F. Haddad, R. Doyle, D. J. Murphy, and S. A. Hunt Right Ventricular Function in Cardiovascular Disease, Part II: Pathophysiology, Clinical Importance, and Management of Right Ventricular Failure Circulation, April 1, 2008; 117(13): 1717 - 1731. [Full Text] [PDF]

				F. Haddad, S. A. Hunt, D. N. Rosenthal, and D. J. Murphy Right Ventricular Function in Cardiovascular Disease, Part I: Anatomy, Physiology, Aging, and Functional Assessment of the Right Ventricle Circulation, March 18, 2008; 117(11): 1436 - 1448. [Full Text] [PDF]

				E. Bedard, D. F. Shore, and M. A. Gatzoulis Adult congenital heart disease: a 2008 overview Br. Med. Bull., March 1, 2008; 85(1): 151 - 180. [Abstract] [Full Text] [PDF]

				P. Khairy, L. Harris, M. J. Landzberg, S. Viswanathan, A. Barlow, M. A. Gatzoulis, S. M. Fernandes, L. Beauchesne, J. Therrien, P. Chetaille, et al. Implantable Cardioverter-Defibrillators in Tetralogy of Fallot Circulation, January 22, 2008; 117(3): 363 - 370. [Abstract] [Full Text] [PDF]

				F. J. Meijboom, J. W. Roos-Hesselink, J. S. McGhie, S. E.C. Spitaels, R. T. van Domburg, L. M.W.J. Utens, M. L. Simoons, and A. J.J.C. Bogers Consequences of a selective approach toward pulmonary valve replacement in adult patients with tetralogy of Fallot and pulmonary regurgitation J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 50 - 55. [Abstract] [Full Text] [PDF]

				P. Khairy and A. J. Marelli Clinical Use of Electrocardiography in Adults With Congenital Heart Disease Circulation, December 4, 2007; 116(23): 2734 - 2746. [Full Text] [PDF]

				A. Uebing, D. G. Gibson, S. V. Babu-Narayan, G. P. Diller, K. Dimopoulos, O. Goktekin, M. S. Spence, K. Andersen, M. Y. Henein, M. A. Gatzoulis, et al. Right Ventricular Mechanics and QRS Duration in Patients With Repaired Tetralogy of Fallot: Implications of Infundibular Disease Circulation, October 2, 2007; 116(14): 1532 - 1539. [Abstract] [Full Text] [PDF]

				A. Gengsakul, L. Harris, T. J. Bradley, G. D. Webb, W. G. Williams, S. C. Siu, N. Merchant, and B. W. McCrindle The impact of pulmonary valve replacement after tetralogy of Fallot repair: a matched comparison Eur. J. Cardiothorac. Surg., September 1, 2007; 32(3): 462 - 468. [Abstract] [Full Text] [PDF]

				S.-C. Yap, J. W. Roos-Hesselink, E. S. Hoendermis, W. Budts, H. W. Vliegen, B. J.M. Mulder, A. P.J. van Dijk, M. J. Schalij, and W. Drenthen Outcome of implantable cardioverter defibrillators in adults with congenital heart disease: a multi-centre study Eur. Heart J., August 1, 2007; 28(15): 1854 - 1861. [Abstract] [Full Text] [PDF]

				R. R Chaturvedi and A. N Redington Pulmonary regurgitation in congenital heart disease Heart, July 1, 2007; 93(7): 880 - 889. [Full Text] [PDF]

				T. M. Bashore Adult Congenital Heart Disease: Right Ventricular Outflow Tract Lesions Circulation, April 10, 2007; 115(14): 1933 - 1947. [Full Text] [PDF]

				P. Anagnostopoulos, A. Azakie, S. Natarajan, N. Alphonso, M. M. Brook, and T. R. Karl Pulmonary valve cusp augmentation with autologous pericardium may improve early outcome for tetralogy of Fallot J. Thorac. Cardiovasc. Surg., March 1, 2007; 133(3): 640 - 647. [Abstract] [Full Text] [PDF]

				E. P. Walsh and F. Cecchin Arrhythmias in Adult Patients With Congenital Heart Disease Circulation, January 30, 2007; 115(4): 534 - 545. [Full Text] [PDF]

				Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) J. Am. Coll. Cardiol., September 5, 2006; 48(5): e247 - e346. [Full Text] [PDF]

				A. Lammers, H. Kaemmerer, R. Hollweck, R. Schneider, P. Barthel, S. Braun, A. Wacker, S. Brodherr-Heberlein, M. Hauser, A. Eicken, et al. Impaired cardiac autonomic nervous activity predicts sudden cardiac death in patients with operated and unoperated congenital cardiac disease. J. Thorac. Cardiovasc. Surg., September 1, 2006; 132(3): 647 - 655. [Abstract] [Full Text] [PDF]

				E. A Shinebourne, S. V Babu-Narayan, and J. S Carvalho Tetralogy of Fallot: from fetus to adult. Heart, September 1, 2006; 92(9): 1353 - 1359. [Full Text] [PDF]

				Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 746 - 837. [Full Text] [PDF]

				U. K. Chowdhury, S. Sathia, R. Ray, R. Singh, K. K. Pradeep, and P. Venugopal 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., August 1, 2006; 132(2): 270 - 277.e4. [Abstract] [Full Text] [PDF]

				T. Karamlou, I. Silber, R. Lao, B. W. McCrindle, L. Harris, E. Downar, G. D. Webb, J. M. Colman, G. S. Van Arsdell, and W. G. Williams Outcomes after late reoperation in patients with repaired tetralogy of fallot: the impact of arrhythmia and arrhythmia surgery. Ann. Thorac. Surg., May 1, 2006; 81(5): 1786 - 1793. [Abstract] [Full Text] [PDF]

				P A Davlouros, K Niwa, G Webb, and M A Gatzoulis The right ventricle in congenital heart disease Heart, April 1, 2006; 92(suppl_1): i27 - i38. [Abstract] [Full Text] [PDF]

S. V. Babu-Narayan