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Ann Thorac Surg 2008;86:1928-1935. doi:10.1016/j.athoracsur.2008.07.019
© 2008 The Society of Thoracic Surgeons
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Original Articles: Pediatric Cardiac

Early Primary Repair of Tetralogy of Fallot in Neonates and Infants Less Than Four Months of Age

Melanie I. Tamesberger, MDa, Evelyn Lechner, MDa, Rudolf Mair, MDb, Anna Hofer, MDc, Eva Sames-Dolzer, MDb, Gerald Tulzer, MD, PhDa,*

a Department of Pediatric Cardiology, General Hospital Linz, Children's Heart Centre Linz, Linz, Austria
b Department of Congenital Heart Surgery, General Hospital Linz, Children's Heart Centre Linz, Linz, Austriaa
c Department of Anesthesia and Intensive Care Medicine, General Hospital Linz, Children's Heart Centre Linz, Linz, Austria

Accepted for publication July 9, 2008.

* Address correspondence to Dr Tulzer, Children's Heart Center Linz, Krankenhausstrasse 26, Linz, 4020, Austria (Email: gerald.tulzer{at}gespag.at).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: The ideal age for correction of tetralogy of Fallot is still under discussion. The aim of this study was to analyze morbidity and mortality in patients who underwent early primary repair of tetralogy of Fallot at the age of less than 4 months and to assess whether neonates, who needed early repair within the first 4 weeks of life, faced an increased risk.

Methods: From 1995 to 2006, 90 consecutive patients with tetralogy of Fallot and pulmonary stenosis underwent early primary repair. Patient charts were analyzed retrospectively for two groups: group A, 25 neonates younger than 28 days who needed early operation owing to duct-dependent pulmonary circulation or severe hypoxemia; and group B, 65 infants younger than 4 months of age who underwent elective early repair.

Results: There was no 30-day mortality; late mortality was 2% after a median follow-up time of 4.7 years. Seven of 88 patients (8%) needed reoperation and twelve of 88 patients (14%) needed reintervention. Groups A and B did not differ significantly in terms of intensive care unit stay, days of mechanical ventilation, overall hospital stay, major or minor complications, or reoperation. Significant differences were found in a more frequent use of a transannular patch (p = 0.045) and more reinterventions (p = 0.046) in group A.

Conclusions: Early primary repair of tetralogy of Fallot can be performed safely and effectively in infants younger than 4 months of age and even in neonates younger than 28 days with duct-dependent pulmonary circulation or severe hypoxemia.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Surgical treatment of tetralogy of Fallot (TOF) was initiated by Blalock and Taussig in 1945 with the establishment of the subclavian artery to pulmonary artery (PA) anastomosis [1]. In 1954, Lillehei and collaborators [2], using controlled cross-circulation in a 10-month-old boy, carried out the first intracardiac repair of TOF, including closure of the ventricular septal defect (VSD) and relief of the RV outflow tract obstruction under direct vision. After this initial success with TOF repair in infancy, however, subsequent attempts of early repair carried a high mortality rate, and the two-stage repair became universally favored.

Owing to advances in anesthetic, operative, and postoperative management, and with growing experience and improvements in cardiopulmonary bypass techniques and myocardial protection, primary repair in early childhood became more common during the 1990s. There are still controversial opinions regarding the optimal time for repair of TOF [3, 4].

Early primary repair is preferred because prolonged hypoxemia and the risk of cyanotic spells are avoided owing to early normalizing of the cardiovascular physiology. Therefore, secondary damage to the heart and other organ systems is minimized [5]. The right ventricle is no longer subject to pressure overload and subsequent RV hypertrophy, which would require a significant amount of surgical resection; that could be a potential substrate for late RV failure and ventricular arrhythmias [6, 7]. Several authors [8, 9] demonstrated that the absolute RV wall thickness decreased significantly after repair before 6 months of age, but did not decrease significantly after 6 months of age.

Early anatomic correction preserves myocardial mechanical and electrical function [10–12] and may also be beneficial to pulmonary angiogenesis and alveologenesis in patients with decreased lung perfusion [3]. Early correction does not increase the risk of late arrhythmias [13, 14] but could even reduce it [15]. In addition, this approach avoids the risks associated with systemic to PA shunting, namely, shunt thrombosis, congestive heart failure, PA distortion, and pulmonary vascular disease.

The postulated disadvantages of primary repair in infants less than 4 months of age include a potential higher risk for organ damage in neonates and young infants undergoing open heart surgery, because of immature organs. For this reason, a later primary repair may be preferred [4].

We have taken the approach of elective primary repair in early infancy in all patients with TOF. If nonsymptomatic, the elective age for surgery was 3 to 4 months at the beginning of the study period and 2 to 3 months during the last 4 years. In symptomatic patients, an early primary repair was performed regardless of the patient's age. The purpose of this study was to analyze our experience with early (younger than 120 days of age) complete repair of TOF. In addition, we wanted to assess the outcome of critically ill neonates who underwent surgery during the first 4 weeks of life owing to progressive cyanosis or duct-dependent lung perfusion, and to compare the surgical outcome of these neonates with that of the older infants.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Between January 1, 1995, and December 31, 2006, 90 consecutive neonates and young infants (aged less than 120 days) with TOF with pulmonary stenosis underwent complete repair. During this time, no other patients less than 4 months of age with TOF were palliated using shunts. There were 57 boys and 33 girls, with a median age at surgery of 49 days (range, 3 to 116). The median weight at surgery was 3.8 kg (range, 2.0 to 6.5 kg). Of these, 7 patients (8%) were premature infants, 11 patients were of low birthweight, less than 2.5 kg, and 2 patients had a birthweight of less than 2 kg.

Preoperative assessment of anatomy and physiology was established with echocardiography alone in all but 2 patients, in whom preoperative cardiac catheterization was thought to be necessary to better define PA anatomy. Pulmonary valve z-score was assessed for less than –2 standard deviations. Patients with pulmonary atresia, absent pulmonary valve, or associated atrioventricular septal defect were excluded. Children with metabolic or genetic disorders were not excluded. Patients were assigned to two groups. Group A consisted of 25 neonates who had either severe hypoxemia (20 of 25) with or without hypoxemic spells or a duct-dependent pulmonary circulation (5 of 25). All these patients underwent early primary repair at an age of 28 days or less (median, 15; range, 3 to 28) with a median weight of 3.3 kg (range, 2.1 to 4.4 kg). Group B consisted of 65 infants who were scheduled for elective surgery before the age of 90 to 120 days (median, 55; range, 30 to 116) with a median weight of 4.0 kg (range, 2.0 to 6.5 kg). Patients of group B who became symptomatic were operated on before their scheduled date of elective surgery.

Cardiac Variations
Anatomic cardiac variations included a right-sided aortic arch in 22 of 90 patients, a left superior caval vein in 8 of 90 patients, and 1 patient with an aberrant right subclavian artery (arteria lusoria). Four patients, all with right aortic arch, had discontinous branch pulmonary arteries: 3 patients had a left PA arising from the left-sided arterial duct, and 1 patient had an absent left PA combined with a hypoplastic left lung.

Coronary Artery Findings
Coronary artery anomalies were found in 7 of 90 patients (8%): 3 patients had a left anterior descending coronary artery from right coronary artery, 1 had a double left anterior descending coronary artery, 1 had a right coronary artery from left anterior descending coronary artery, 1 had a single left coronary artery (right coronary artery from left coronary artery), and 1 had a left anterior descending coronary artery from left circumflex coronary artery.

Extracardiac malformations were found in 21 of 90 patients (23%), and are given in detail in Table 1. A syndrome was diagnosed in 13 of 90 patients (14%), including 6 patients with 22q11 deletion, 4 patients with trisomy 21, 2 patients with VACTERL (abnormalities of vertebrae, anus, cardiovascular tree, trachea, esophagus, renal system, and limb buds), and 1 Goldenhar syndrome, all in group B.


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  		Table 1 Extracardiac Malformations
 
Data were retrieved retrospectively from medical records, and echocardiographic and surgical reports. The data analyzed are listed in Table 2. This study was approved by the local Ethics Committee. The need for obtaining patient consent was waived because individual patients are not identified.


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  		Table 2 Data Reviewed
 
Surgical Technique
Standard neonatal and infant techniques of cardiopulmonary bypass were employed. Double venous cannulation and moderate hypothermia were used in all cases. Cold crystalloid cardioplegia was used for cardiac arrest. The ventricular septal defect (VSD) was closed with a Dacron (C.R. Bard, Haverhill, Pennsylvani) or glutaraldehyde-treated autologous pericardial patch. Transventricular repair was carried out with limited ventriculotomy, minimal myectomy, and transsection of obstructive trabeculae. Eighty-four transventricular repairs and 6 transatrial-transpulmonary repairs were performed. The pulmonary valve annulus was divided and enlarged by means of a transannular patch made of autologous glutaraldehyde-treated pericardium in 59 of 90 patients (66%): in group A, 21 of 25 patients (84%); and in group B, 38 of 65 (58%). The decision whether to use a transannular patch was made intraoperatively by the surgeon. The pulmonary valve annulus was measured using a Hegar's dilator as probe. If the z-score of the pulmonary valve annulus was –2.0 or less, the decision was made to use a transannular patch. The transannular patch was extended onto the proximal left PA and just across the orifice of the right PA. Branch pulmonary arterioplasty was performed if there was intraoperative evidence of branch PA stenosis. This was necessary in only 2 patients. In the patients with discontinuous branch PAs, the left PA was implanted directly into the side of the main PA after resection of the ductal tissue. The foramen ovale was deliberately left open to prevent eventual early postoperative low cardiac output due to right heart failure by allowing trial right to left shunting. Right ventricular (RV) and PA pressures were measured routinely intraoperatively to assess residual gradients. Transesophageal or transthoracic echocardiography was not used routinely. Intracardiac lines were placed in the left atrium and in the PA to allow precise postoperative monitoring.

Follow-Up
Before discharge from the hospital, echocardiography was performed in all patients. Follow-up visits were scheduled 2 weeks, 6 weeks, and 3 months after operation, and thereafter, every 6 to 12 months.

Statistical Methods
Concerning hospital stay, intensive care unit stay, and duration of mechanical ventilation, missing values because of death were replaced according to the worst-case principle. All other data sets were complete.

All metric variables were tested for a normal distribution (test of normality: Kolmogorov-Smirnov with Lilliefors significance correction, type I error = 5%). For the subgroup comparison of the only normally distributed metric variable (duration of aortic cross-clamp), the t test for independent samples was used. The other metric variables showed a significant deviation from normal distribution. Group comparisons of the other metric variables were performed using a nonparametric test (Mann-Whitney U test). Categorical variables were compared by {chi}2 or Fisher's exact test. All tests are two-tailed with a confidence level of 95% (p < 0.05). No adjustments for the p values (such as Bonferroni corrections) were made; therefore, the concerning p values are only descriptive.

For the analysis of differences in the course of survival (presented as Kaplan-Meier survival curves), the log-rank test was used.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Operative Data
Operative and postoperative data for all patients and the comparison between groups A and B are shown in Table 3. Only two variables turned out to be significantly different between the groups, namely, rate of reinterventions (higher in group A) and use of a transannular patch (higher in group A). All other variables did not reach statistical significance.


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  		Table 3 Operative and Postoperative Data
 
Overall, the median cardiopulmonary bypass time was 131.5 minutes (range, 92 to 252), and the mean aortic cross-clamp time was 65 ± 15 minutes. Statistical analyses showed no significant difference in cardiopulmonary bypass time and aortic cross-clamp time between groups.

Only 6 of 90 patients (7%) had a transatrial-transpulmonal correction; 84 of 90 patients (93%) needed a transventricular correction. Transannular patches were more frequently needed when repair was done in neonates compared with older infants (84% versus 58%; p = 0.027). Seven of 90 patients (8%), all group B, only needed muscle resection without placement of an infundibular patch for release of the RV outflow tract obstruction. Delayed sternal closure was performed in 3 of 90 patients (3%). Only 1 patient, corrected at the 12th day of life, required a RV-PA conduit, owing to a coronary artery anomaly (left anterior descending coronary artery arising from right coronary artery).

Mortality
There was no 30-day mortality in either group. Late death occurred in 2 of 90 patients (2%), both in group B, and were not related to the operation. One patient died on the 43rd postoperative day of hypoplastic lungs complicating a large congenital umbilical hernia. The second patient was diagnosed as having VACTERL association with severe hypoplasia of the left lung. This patient had severe postoperative pulmonary hypertension and died on postoperative day 68 of right heart failure and respiratory failure. In our opinion, because pulmonary hypertension was the result of lung hypoplasia, a modified Blalock-Taussig shunt in this situation most likely would not have changed the prognosis significantly. So far, there have been no late deaths after hospital discharge. The overall survival rate at a median follow-up time of 4.7 years is 98% (88 of 90).

Complications
Major complications were found in 5 of 90 patients (6%), 2 (8%) in group A, and 3 (5%) in group B. There was 1 patient with septic shock and acute renal failure on postoperative day 5. One patient had a severe systemic inflammatory response syndrome and was treated with vasopressin. Junctional ectopic tachycardia required treatment with amiodarone and external pacing in another patient. Two patients had severe pulmonary hypertension and prolonged mechanical ventilation due to hypoplastic lungs. Postoperative intracerebral bleeding due to surgery was not observed.

Minor complications included diaphragmatic paralysis, pericardial effusion requiring drainage, intermittent supraventricular tachycardia, residual VSD, mild renal failure without dialysis, thrombotic formation on an atrial line, thrombotic occlusion of a femoral vein, mechanical hemolytic anemia due to a residual VSD in a patient with Dacron patch, uncomplicated cerebral seizures, and pneumothorax.

Diaphragmatic paralysis was observed in 4 of 90 patients (4%), 3 right sided and 1 left sided. Residual VSDs were found in 2 of 88 patients (2%). In 1 patient, the residual VSD was hemodynamically significant and required surgical closure 13 months later.

Follow-Up
The median follow-up time was 56 months (range, 4 to 146), and no patient was lost to follow-up. Data about reoperation are given in Table 4: in all, 7 of 88 patients (8%) required a reoperation, 3 patients of group A and 4 patients of group B. So far, only 2 patients needed a RV-PA conduit. In the first patient, a primary repair using an outflow tract patch and a pulmonary valvulotomy was performed, despite a borderline small pulmonary valve due to a coronary artery anomaly. After unsuccessful dilation of a residual pulmonary valve stenosis, an implantation of a RV-PA homograft was performed 12 months after primary operation. The second patient had severe pulmonary regurgitation early after repair with a transannular patch because of hypoplastic lungs and persistent increased pulmonary vascular resistance. Freedom from reoperation was 92% (81 of 88 patients) at 5 years (Fig 1).


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  		Table 4 Reoperation Data
 

Figure 1
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  		Fig 1. Freedom from reoperation. Number of remaining patients: at 0 months, 25 group A and 65 group B; at 30 months, 14 group A and 45 group B; at 60 months, 12 group A and 22 group B; and at 90 months, 5 group A and 13 group B.

 
Reintervention data are given in Table 5: in all, 12 patients needed cardiac catheterization with a total of 22 interventions during follow-up. The most common reason for intervention was a stenotic left PA that had to be stented or dilated (9 of 12). Freedom from reintervention was 86% (76 of 88) at 5 years (Fig 2). Patients of group A had a significantly higher rate of reinterventions than did patients of group B (28% versus 8%, p = 0.018).


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  		Table 5 Reintervention Data
 

Figure 2
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  		Fig 2. Freedom from reintervention. Number of remaining patients: at 0 months, 25 group A and 65 group B; at 30 months, 14 group A and 45 group B; at 60 months, 12 group A and 22 group B; and at 90 months, 5 group A and 13 group B.

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
Our data demonstrate that early primary repair can be performed safely and effectively in neonates and infants less than 4 months of age with TOF with pulmonary stenosis. One of the main arguments against early elective repair is a potential higher operative risk. Among our patients, there was no 30-day mortality, and the 2 late deaths were not related to cardiac surgery. These results are in agreement with the study of Reddy and coworkers [3], who showed excellent early and midterm results with routine primary repair of TOF in infants less then 3 months of age. Additionally, Pigula and colleagues [13] found a low mortality rate associated with early complete TOF repair; and Cobanoglu and coworkers [16] showed that age less than 3 months does not affect operative survival.

Children with TOF usually have a high rate of extracardiac anomalies and syndromes [17], which are thought to further increase the risk of open heart surgery. Although our study patients had a high rate of extracardiac anomalies and syndromes, with 23% and 14%, respectively, these factors did not influence 30-day-mortality nor did associated cardiac or coronary anomalies.

Premature infants and neonates, especially those with severe cyanosis or duct-dependent pulmonary circulation, represent a group of patients for whom open heart surgery is frequently postponed in favor of palliative procedures that can be carried out without cardiopulmonary bypass to reduce mortality and morbidity. Van Arsdell and associates [4] found that infants less than 3 months of age had a higher morbidity rate compared with older infants and had a more frequent need for a peritoneal drainage (47%), a longer time to extubation, and longer stays in the intensive care unit and hospital (16 days). In our study, we had shorter times in all of these categories, and we could not find any statistically significant difference regarding mortality, early morbidity, major or minor postoperative complications, days of mechanical ventilation, and time spent in the intensive care unit or hospital between our "high-risk" group and those patients, who had elective repair later, until the age of 4 months. This result is probably due to recent advances in surgical and perfusion techniques as well as to improved postoperative pediatric intensive care.

The relatively high incidence of ascites drainage, in 11 of 90 patients (12%), is probably influenced by our policy to drain even moderate amounts of ascites, especially in situations of patients with low urinary output. Time until chest tube removal was prolonged, probably because of maintaining higher filling pressures in the presence of RV hypertrophy, and tended to be longer in older patients.

Another argument against neonatal repair is that the smaller the child, the more technically challenging a surgical procedure becomes, resulting in longer surgery time with all the resulting consequences. In contrast, we found that the younger patient group (group A) had neither a longer aortic cross-clamp time nor a longer cardiopulmonary bypass time, which indicates that there was no surgical technical limitation to performing early primary repair of TOF in neonates. During the study period, there was no significant difference between groups A and B concerning the rate of reoperations; however, the follow-up period was rather short.

Further, significant differences between groups A and B were found in the higher rate of reinterventions and a more frequent need of a transannular patch. The most common reason for a reintervention was significant pulmonary stenosis, which was present in 9 patients (10%). Kinking and stenosis of the left PA is a common and well-described problem in children with TOF, and is attributed to the special anatomy of the pulmonary arteries in this situation. The prevalence in our cohort fits well with that of other reported series [18]. Both reflect the more severe anatomical situation of these early symptomatic patients. This observation is in accordance with previously published data [15, 19], which also showed that the need for a transannular patch reflects the severity of the RV outflow tract obstruction at the annular level. Consequently, patients in whom a transannular patch was used were at the more severe end of the morphologic spectrum [20]. Symptomatic patients selected for repair in the neonatal period generally have severe hypoplasia of the pulmonary valve annulus and have received a transannular patch because of the morphology, not because of their age.

Concerning the long-term outcome, several authors [20, 21] reported that the use of a transannular patch did not reduce late survival and was associated with a lower incidence of RV outflow tract obstruction. Our midterm follow-up data after a median of 4.7 years confirm this observation. Of our patient population, 59 of 90 patients (66%) received transannular patches, and in this group, so far there has been no residual RV outflow tract obstruction observed.

A significant problem of transannular patches, however, is the increasing RV dilation and subsequent RV failure due to severe pulmonary regurgitation. A large amount of experimental work has been published that demonstrates the deleterious effects of chronic pulmonary regurgitation on RV function, RV volume, and exercise performance [22, 23]. On the other hand, d'Udekem and colleagues [24] found that transannular patching and RV outflow tract patching equally affected RV function. So far, only 1 study patient who underwent repair by use of a transannular patch received a valved RV-PA conduit because of RV volume overload.

Limitations
The follow-up time is too short for conclusions regarding the effect of early primary repair for the development of late arrhythmias or RV dysfunction.

In conclusion, early primary repair of TOF with pulmonary stenosis can be performed safely and effectively for young infants at an age of less than 4 months as well as for critically ill neonates. Repair during the first 4 weeks of life because of severe cyanosis or duct-dependent pulmonary circulation was associated with more frequent use of a transannular patch and an increased rate of reinterventions, reflecting anatomic severity. Long-term follow-up data are needed to assess the effects of early relief of cyanosis, RV pressure overload, and less muscle resection in the right ventricular outflow tract regarding late RV failure and arrhythmias as well as the need for pulmonary valve replacement after early correction with a transannular patch.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
The study was supported by the Medical Society of Upperaustria (Medizinische Gesellschaft für Oberösterreich) and the GESPAG (Gesundheits-und-Spitals AG).


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Castaneda AR, Jonas RA, Mayer JE, Hanley FL. Cardiac surgery of the neonate and infantPhiladelphia: WB Saunders; 1994. pp. 215-234.
  2. Lillehei CW, Cohen M, Warden HE, et al. Direct vision intracardiac surgical correction of the tetralogy of Fallot, pentalogy of Fallot and pulmonary atresia defects: report of the first ten cases Ann Surg 1955;142:418-442.[Medline]
  3. 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;60:592-596.
  4. Van Arsdell GS, Maharaj GS, Tom J, et al. What is the optimal age for repair of tetralogy of Fallot? Circulation 2000;102(Suppl 3):123-129.[Free Full Text]
  5. Touati GD, Vouhe PR, Amodeo A, et al. Primary repair of tetralogy of Fallot in infancy J Thorac Cardiovasc Surg 1990;99:396-403.[Abstract]
  6. Derby CD, Pizarro C. Routine primary repair of tetralogy of Fallot in the neonate Expert Rev Cardiovasc Ther 2005;3:857-863.[Medline]
  7. Walsh EP, Rockenmacher S, Keane JF, Hougen TJ, Lock JE, Castaneda AR. Late results in patients with tetralogy of Fallot repaired during infancy Circulation 1988;77:1062-1067.[Abstract/Free Full Text]
  8. Seliem MA, Wu YT, Glenwright K. Relation between age at surgery and regression of right ventricular hypertrophy in tetralogy of Fallot Pediatr Cardiol 1995;16:53-55.[Medline]
  9. Hirsch JC, Mosca RS, Bove EL. Complete repair of tetralogy of Fallot in the neonate: results in the modern era Ann Surg 2000;232:508-514.[Medline]
  10. Nakazawa M, Shinohara T, Sasaki A, et al. Arrhythmias late after repair of tetralogy of Fallot: a Japanese multicenter study Circ J 2004;68:126-130.[Medline]
  11. 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;36:2279-2283.[Abstract/Free Full Text]
  12. Harrison DA, Siu SC, Hussain F, MacLoghlin CJ, Webb GD, Harris L. Sustained atrial arrhythmias in adults late after repair after tetralogy of Fallot Am J Cardiol 2001;87:584-588.[Medline]
  13. Pigula FA, Khalil PN, Mayer JE, del Nido PJ, Jonas RA. Repair of tetralogy of Fallot in neonates and young infants Circulation 1999;100(Suppl 2):157-161.
  14. Deanfield JE, McKenna WJ, Presbitero P, England D, Graham GR, Hallidie-Smith K. Ventricular arrhythmias in unrepaired and repaired tetralogy of Fallot: relation of age, timing of repair, and haemodynamic status Br Heart J 1984;52:77-81.[Abstract/Free Full Text]
  15. Knott-Craig CJ, Elkins RC, Lane MM, Holz J, McCue C, Ward KE. A 26-year experience with surgical management of tetralogy of Fallot: risk analysis for mortality or late reintervention Ann Thorac Surg 1998;66:506-511.[Abstract/Free Full Text]
  16. Cobanoglu A, Schultz JM. Total correction of tetralogy of Fallot in the first year of life: late results Ann Thorac Surg 2002;74:133-138.[Abstract/Free Full Text]
  17. Michielon G, Marino B, Formigari R, et al. Genetic syndromes and outcome after surgical correction of tetralogy of Fallot Ann Thorac Surg 2006;8:968-975.
  18. Hennein HA, Mosca RS, Urcelay G, Crowley DC, Bove EL. Intermediate results after complete repair of tetralogy of Fallot in neonates J Thorac Cardivasc Surg 1995;109:332-344.[Abstract/Free Full Text]
  19. Kirklin JK, Kirklin JW, Blackstone EH, Milano A, Pacifico AD. Effect of transannular patching on outcome after repair of tetralogy of Fallot Ann Thorac Surg 1989;48:783-791.[Abstract/Free Full Text]
  20. Bacha EA, Scheule AM, Zurakowski D, et al. Long-term results after early primary repair of tetralogy of Fallot J Thorac Cardiovasc Surg 2001;122:154-161.[Abstract/Free Full Text]
  21. Murphy JG, Gersh BJ, Mair DD, et al. Long term outcome in patients undergoing surgical repair of tetralogy of Fallot N Engl J Med 1993;329:593-599.[Medline]
  22. Eyskens B, Reybrouck T, Bogaert J, et al. Homograft insertion for pulmonary regurgitation after repair of tetralogy of Fallot improves cardiorespiratory exercise performance Am J Cardiol 2000;85:221-225.[Medline]
  23. Jonsson H, Ivert T, Jonasson R, Holmgren A, Björk VO. Work capacity and central hemodynamics thirteen to twenty-six years after repair of tetralogy of Fallot J Thorac Cardivasc Surg 1995;110:416-426.[Abstract/Free Full Text]
  24. d‘Udekem Y, Ovaert C, Grandjean F, et al. Tetralogy of Fallot: transannular and right ventricular patching equally affect late functional status Circulation 2000;102:116-122.

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