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Ann Thorac Surg 2006;81:1786-1793
© 2006 The Society of Thoracic Surgeons
a Divisions of Cardiovascular Surgery and Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada
b Division of Cardiology, Toronto Congenital Cardiac Center for Adults, Toronto, Ontario, Canada
Accepted for publication December 9, 2005.
* Address correspondence to Dr Williams, Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada (Email: bill.williams{at}sickkids.ca).
Presented at the Fifty-second Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 10–12, 2005.
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Abstract |
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METHODS: Review was performed of all ToF patients from 1969 to 2005 undergoing reoperation late (>1 year) after repair. Patients with associated lesions, except pulmonary atresia, were included. A total of 249 patients had 278 reoperations. Procedures at initial reoperation included pulmonary valve replacement (PVR) in 217, ablation in 63, and tricuspid valve repair/replacement in 46. Pre-reoperative arrhythmias were present in 75, including supraventricular tachycardia (SVT) in 31, ventricular tachycardia (VT) in 34, and SVT+VT in 10 patients.
RESULTS: Median age at reoperation was 23 years (range, 1 to 63). Ten-year survival after reoperation was 93%, and was independent of arrhythmia status (p = 0.86). Arrhythmia patients were characterized by older age at initial repair and at late reoperation, tricuspid and pulmonary regurgitation, and longer QRS duration (p < 0.001 for all). Risk factors for post-reoperative recurrent arrhythmia were longer QRS duration and not having PVR. Longer QRS duration, with a cut-point of more than 160 msec, was associated with recurrent SVT (p = 0.004). Supraventricular tachycardia ablation improved arrhythmia-free survival (75% versus 33%, p < 0.001) but VT ablation did not (96% versus 95%, p = 0.50). However, recurrent VT occurred in only 3 patients (10%).
CONCLUSIONS: Late mortality in patients undergoing reoperation after ToF repair is not impacted by pre-reoperative arrhythmia. Prolongation of QRS identifies patients at risk for recurrent VT and SVT, but recurrent VT is uncommon. Early PVR, and surgical ablation in patients with SVT, decreases arrhythmic risk.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Definition of Arrhythmia
Significant arrhythmia was defined as (1) sustained atrial flutter or fibrillation, termed supraventricular tachycardia (SVT), or sustained ventricular tachycardia (VT) documented on 12-lead electrocardiogram, Holter recording, or electrocardiographic strips; or (2) palpitations associated with syncope or near syncope in patients subsequently found to have inducible sustained SVT or sustained VT at electrophysiologic testing. Sustained was defined as arrhythmia lasting more than 30 seconds or of any length of time if associated with hemodynamic compromise.
Echocardiographic Analysis
Pre-reoperative (n = 109) and postoperative (most recent; n = 134) two-dimensional color Doppler and M-mode echocardiographic reports were reviewed. The severity of pulmonary regurgitation was assessed by pulse-wave Doppler characteristics and color flow mapping as previously described [14], and was graded as none, mild, moderate, or severe. Tricuspid regurgitation was also graded according to standard technique. Right ventricular function was subjectively graded as normal, mildly reduced, moderately reduced, or severely reduced.
Surgical Technique
Pulmonary valve replacement (PVR) was performed as previously described [15]. Techniques of insertion included orthotopic in situ valve placement in 82% and conduit insertion in 18%. Prosthetic valve type was known in 213 patients, including 139 porcine valves, 37 pericardial valves, 29 homograft valves, and 8 polystan valves.
Management of ventricular tachycardia
Patients with VT underwent intraoperative electrophysiologic mapping as described by Downar and colleagues [16, 17] using a customized right ventricular balloon electrode array for recording endocardial activation and a second electrode array positioned over the surface of the heart for epicardial recording (Fig 1). Simultaneous recording of endocardial and epicardial activation from 224 sites were displayed using a multiplex recording system [16, 17]. Induction of VT was performed using a standard pacing protocol from the right ventricular apex. After induction and mapping, patients with monomorphic VT were cryoablated using a 1.5-cm tip cryoprobe applied to the macroreentry site for 2 minutes at -60°C during cardioplegic arrest of the heart. Patients who had multifocal VT (n = 3) or those who could not be induced (n = 5) were not ablated.
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Data Analysis
Data are presented as frequency, median with range, or mean ± SD as appropriate. Percentages, hazard functions, and parametric estimates are presented with confidence limits equivalent to one standard error (68%). All data analyses were performed using SAS statistical software (version 9; SAS Institute, Cary, North Carolina). Categorical variables were analyzed by the 
2 test or Fisher's exact test. Continuous variables between groups were compared using 2-sample t tests or the Wilcoxon rank-sum test, depending upon the normality of the data. Pair-wise comparisons of continuous variables within each group were performed using a paired t test or Wilcoxon sign rank test. Time-related events were analyzed initially using the nonparametric Kaplan-Meier method. Multiphase parametric modeling of the underlying hazard function was then used to determine rates of transition to time-related events and identify incremental risk factors associated with each transition rate, as previously described [20]. Multiple imputation techniques were used for missing data, with missing value flags created to account for potential bias. Transformations to optimize calibration to risk for continuous predictors and interactions among retained variables in the model were considered in all multivariable analyses. Variable selection was primarily by bootstrap bagging, with those having greater than 50% reliability included in the final models [20].
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Results |
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Patients with arrhythmia who were palliated (n = 42) were older at palliation compared with those without arrhythmia. Arrhythmia patients were also older at the age of complete repair and at reoperation. However, the youngest patients at the time of repair, those with absent pulmonary valve (median age, 4.1 years; range, birth to 15.1 years) and atrioventricular septal defect (median age, 3.7 years; range, 7 months to 11.1 years), were present only in the nonarrhythmia group. Moderate or greater pulmonary regurgitation was more prevalent in those with arrhythmia as was the prevalence of a combination of moderate or greater tricuspid and pulmonary regurgitation. The QRS duration before reoperation was longer in arrhythmia patients compared with patients who did not have arrhythmia. Patients with mild or greater right ventricular dysfunction on echocardiography before reoperation (n = 10) had longer QRS duration (165 ± 24 msec) than patients with normal right ventricular function (n = 38; 142 ± 31 msec; p = 0.02). The QRS duration before reoperation was similar among those with SVT (178 ± 21 msec) and those with VT (179 ± 22 msec).
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Two ablation procedures were performed at a subsequent (second) reoperation. Aneurysm resection (28% versus 13%, p = 0.006) and tricuspid valve repair/replacement (32% versus 13%, p < 0.001) were more commonly performed in patients with arrhythmias than in patients without arrhythmia.
There were 13 deaths during the study period, occurring at a median interval of 4.1 years (range, 0 to 16) after late reoperation. Two of these were in-hospital deaths: one, a complex patient with SVT at reoperation who hemorrhaged after replacement of the ascending aorta, PVR, and isthmus cryoablation; and the other, a patient who was arrhythmia free and died of iatrogenic right coronary artery occlusion.
Overall survival after late reoperation was 94% (70% confidence interval: 92% to 95%) at 10 years after late reoperation and was independent of arrhythmia status (p = 0.86; Fig 2). The only risk factor for death identified on multivariable analysis was older age at intracardiac repair (p < 0.001; Table 3).
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A total of 59 patients had 65 ablative operations for arrhythmia (Fig 3). Two ablations occurred at the subsequent (second) reoperation: one patient first underwent tricuspid valve replacement and then underwent ablation of SVT, and another had a second VT ablation procedure. There were 28 patients who had isolated SVT ablation, with the majority undergoing cryoablation of the isthmus. Ablation of VT only was performed in 25 patients, and 6 patients had intervention for both SVT and VT.
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Late arrhythmias in patients without pre-reoperative arrhythmia
Late arrhythmias were documented at last follow-up in 14 of the 174 patients who did not have pre-reoperative arrhythmia. Late arrhythmias in this group were SVT in 10, VT in 2 patients, and unknown type in 2 patients.
Current Status
Echocardiographic and electrocardiographic data were available in 164 patients at a median of 4.3 years (range, 0 to 23) after reoperation. Mean peak systolic gradient across the pulmonary valve was 21 ± 9 mm Hg. Stabilization of the QRS duration was noted in patients having PVR (163 ± 29 preoperatively versus 166 ± 22 postoperatively) compared with patients not undergoing PVR (133 ± 15 preoperatively versus 153 ± 12 postoperatively; p = 0.05).
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Mortality
We observed no difference in overall mortality between patients presenting with or without arrhythmia at the time of late reoperation. However, that may reflect both the potential benefit conferred by arrhythmia surgery and the infrequency of sustained ventricular tachycardia in this study cohort, as ventricular arrhythmias are known to be a common mechanism of late death in patients after ToF repair [4–9]. Concordant with previous reports [8, 4, 21], we identified older age at repair as a risk factor for overall death. Long-standing cyanosis adversely affects myocardial performance, a finding supported by the increased incidence of left ventricular dysfunction in patients repaired after age 9 years [21–23]. Furthermore, older age at repair is a potential surrogate for earlier era of operation when techniques of repair and myocardial preservation were not optimal. Recent modifications in surgical technique, such as the transatrial/transpulmonary approach, have led to improved early outcomes [24, 25]. Nevertheless, our data provide additional evidence that early intracardiac repair, when feasible, is associated with durable long-term benefit.
Reducing the Risk of Arrhythmia Recurrence
Prolonged QRS duration (> 180 msec) is associated with electrophysiologically inducible ventricular tachycardia [7, 8] and adverse arrhythmic events such as sudden death [5, 7, 8]. Mechanoelectrical interaction, whereby a dilated right ventricle provides the substrate for electrical instability, underlies the propensity toward ventricular arrhythmia [5, 7, 8]. Chronic pulmonary regurgitation is the predominant associated lesion, and has been correlated with increased end-diastolic volume and an increased incidence of ventricular arrhythmia [26]. We recently showed that similar structural and hemodynamic abnormalities, including a larger right atrial volume and right ventricular chamber size, are also related to atrial arrhythmias in patients after ToF repair [9]. The present study demonstrates that prolongation of the QRS duration, especially beyond 160 msec, increases the risk of atrial arrhythmias, and provides further evidence that a similar underlying mechanism is responsible for both atrial and ventricular arrhythmias in postrepair ToF patients.
Replacement of the pulmonary valve was protective against the development of recurrent arrhythmias in the present study. The salutary effects of early PVR may be related to a reduction of the QRS duration, as documented by a recent study by Hooft van Huysduyen and colleagues [27], or perhaps stabilization of the QRS duration, as shown by Therrien and colleagues [15]. Pulmonary valve replacement was associated with stabilization of the QRS duration in this study, in keeping with the longer duration of follow-up (median 4.3 years) compared with the study by Hooft van Huysduyen, in which median follow-up was only 14 months [27]. Our data, and those from Hooft van Huysduyen and coworkers [27] suggest that liberalization of current criteria for PVR (namely, symptomatic patients with exercise intolerance, clinical arrhythmia, or severe RV dilation) may lead to reduced arrhythmia vulnerability.
The type of ablative surgery was not associated with the risk of recurrent arrhythmia, although others have shown that a modified right-sided maze procedure is superior to anatomic isthmus block in treating reentrant atrial arrhythmias [28]. Management paradigms for atrial arrhythmia at our center have evolved from isthmus block to a right-sided maze procedure for patients with atrial flutter, and a biatrial maze for those with atrial fibrillation.
We recognize that in the absence of hemodynamic problems, atrial arrhythmias are often treated successfully using radiofrequency catheter ablation. The results of catheter ablation for ventricular tachycardia in patients late after repair of ToF are less conclusive. Previous reports by Oda and associates [29] and Gonska and associates [30] have demonstrated the feasibility of catheter ablation in patients with right ventricular outflow tract tachycardia late after repair of ToF without recurrence in the short term, but Morwood and associates [31] showed a high recurrence rate of 38% at 3.8 years. Our current algorithm does include routine preoperative electrophysiologic study testing in postrepair ToF patients with VT. Certainly, attempts at catheter ablation would be reasonable provided that stable monomorphic VT is induced for precision mapping and anatomic obstacles (His bundle or coronary arteries) are absent. However, in the late postrepair ToF patient, arrhythmia surgery (or integration of the principles of catheter ablation into the surgical repair) may be preferable to isolated catheter ablation of VT given that operative restoration of RV structure and function may contribute more to the reduction in recurrent VT risk.
Indications for implantable cardioverter defibrillator therapy in this population have been described [32]. These include implantation in patients with a widened QRS (> 180 msec), especially in the setting of reduced ventricular function, nonsustained VT, or late potentials and inducible sustained monomorphic VT despite surgical correction of all hemodynamic abnormalities and either catheter or surgical ablation.
Limitations
Our analysis has the limitations of any retrospective single institution experience spanning a long time period, including referral bias, selection bias, and missing data. Moreover, we used an unselected group of patients to minimize potential bias, and therefore included all patients undergoing reoperation late after ToF repair, recognizing that doing so would increase heterogeneity within our cohort. The QRS duration was not manually measured, but was obtained from computer-generated reports present in the medical record. Echocardiography has well-known limitations in the assessment of right ventricular function and geometry, especially in the presence of a right ventricular outflow patch. Lack of uniform availability precluded the use of more sensitive magnetic resonance imaging–derived right ventricular volume measurements in our analysis. Finally, identification of the optimum ablation technique for atypical flutter or atrial fibrillation was obviated because no patients in this study underwent a biatrial maze procedure.
In conclusion, late mortality in patients requiring reoperation after ToF repair is not affected by arrhythmia, but is decreased by a strategy of early primary repair. Prolongation of QRS is a useful marker to identify patients at risk for both atrial and ventricular arrhythmias. Timely PVR, and surgical ablation in patients with SVT, decreases the risk of recurrent arrhythmia.
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Discussion |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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The first question is, what is the numerator? What percent of all patients with Tetralogy of Fallot will end up being reoperated over a long period of time? So your 249 patients who had a reoperation for tetralogy is the numerator? This is out of how many patients had a Tetralogy of Fallot repair in that period from 1969 to 2005?
DR KARAMLOU: Although I can't give you an exact number, I can tell you that the majority of patients who actualy underwent pulmonary valve replacement, of whom the vast majority were post-repair tet survivors, is actually nearly 1,000 patients. We are a referral center and certainly there is a degree of referral bias to our institution, but I think that that probably represents a slight underestimation of reoperations. So probably it is about 50%.
DR TCHERVENKOV: The second question refers to the fact you alluded to, that pulmonary valve replacement (PVR) seemed to stabilize the increasing QRS duration. But when I looked at the data from your slides, the patients with PVR versus no PVR had significantly different QRS durations before the placement of a valve. So I think it would be erroneous or misleading to make that inference. Have you looked at patients with comparable QRS, two subgroups of patients, comparable QRS duration, before valve implantation, and then seeing what the effect of valve implantation was? It is possible there is a ceiling effect. Once you have a very long QRS, how much longer can you make it?
DR KARAMLOU: I think that is true, and I think partly that inference was drawn by results from Dr Thierrien from her work at our institution. She has published over three papers in that regard. I can say that QRS duration was entered as a multivariable factor and it was adjusted for the initial QRS duration. So I certainly think while you are correct, that the patients who had an increased QRS duration started out at a lower value and perhaps their trajectory then can be greater over time. But the other thing is that increased QRS duration certainly impacts the outcome in these patients, and I think that there is ample historical evidence to probably support that inference.
DR TCHERVENKOV: And the final question regards the indication for pulmonary valve placement in this study, because there are centers that have a lower threshold for pulmonary valve implantation and other centers have a higher threshold. What were the indications for reoperation in these patients, and more specifically, what was the indication for pulmonary valve implantation in your center? Was it size of the right ventricle, was it functional status of the patient, was it the presence of both pulmonary and tricuspid regurgitation? Can you elucidate the issue of indications?
DR KARAMLOU: Yes. It is an evolving paradigm and I don't think that there are any completely agreed-upon criteria. At our institution, if the right ventricular end-diastolic volume is about 185 mL/m2 or the end-systolic volume is around 85, certainly that would be an indication that probably a pulmonary valve replacement would be beneficial based on historical evidence that normalization of right ventricular volumes does not occur if you operate later than that point. Certainly symptoms are also an important factor, and tricuspid valve regurgitation and increased QRS duration beyond 180 msec would also be accepted criteria at our hospital.
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