(Circulation. 1999;100:II-157.)
© 1999 American Heart Association, Inc.
Surgery for Congenital Heart Disease |
Repair of Tetralogy of Fallot in Neonates and Young Infants
From the Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Mass.
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Abstract |
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Background—The timing of repair of tetralogy of Fallot (TOF) remains controversial. Advantages to early complete repair include removal of right ventricular outflow tract obstruction, alleviation of systemic hypoxia, and avoidance of palliation with an arteriopulmonary shunt.
Methods and Results—This is a retrospective review of 99 children with TOF pulmonary stenosis (TOF/PS) or TOF pulmonary atresia (TOF/PA) who were <90 days of age undergoing early complete repair. Fifty-nine were prostaglandin E dependent, and 91% of neonates were symptomatic at the time of repair. Univariate and multivariate analyses of patient characteristics, anatomic features, and operative management showed the diagnosis of TOF/PA and smaller body surface area to be the only independent risk factors for death. Early mortality was 3% (3 of 99), and actuarial survival rates were 94% at 1 year and 91.6% at 5 years. Freedom from catheterization was 86% at 1 year and 73% at 5 years. Patients repaired for TOF/PA had a significantly lower freedom from reoperation than did those repaired for TOF/PS.
Conclusions—Early complete TOF repair can be accomplished with a low mortality. Children with TOF/PA repaired had a lower freedom from reoperation that did those with TOF/PS. Longer follow-up, with emphasis on arrhythmias and right ventricular function, is required to define the long-term benefits of early repair.
Key Words: tetralogy of Fallot • surgery • pediatrics
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Introduction |
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The optimal surgical management of neonates and infants with tetralogy of Fallot (TOF) remains controversial. Evidence suggests that early repair of congenital heart disease minimizes the secondary damage to the heart and other organ systems.1 2 3 4 5 This realization, along with significant advances in anesthetic, operative, and postoperative management, has been the stimulus for early primary repair of TOF. However, although early surgical repair has been adopted in many centers, a 2-staged repair (arteriopulmonary shunt with subsequent repair) remains favored by some.
Advantages of early anatomic correction include removal of the stimulus for right ventricular hypertrophy, alleviation of cyanosis, and preservation of myocardial mechanical and electrical function. In addition, this approach avoids the risks of pulmonary artery shunting with its inherent risks, namely shunt thrombosis, congestive heart failure, pulmonary artery distortion, or pulmonary vascular disease. Since DiDonato et al 6 first reported the Boston Children’s Hospital experience with neonatal repair of TOF, early repair has been the institutional standard for these patients. The purpose of this retrospective review is to describe our subsequent experience with early (<90 days of age) complete repair of tetralogy of Fallot.
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Methods |
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Between January 1, 1988, and December 31, 1996, 99 neonates and young infants (age <90 days) underwent complete repair of TOF with pulmonary stenosis (TOF/PS, n=73) and pulmonary atresia (TOF/PA, n=26). Data were obtained from the cardiac database and review of medical records. Preoperative diagnosis and evaluation routinely included echocardiographic examination. When preoperative evaluation suggested confluent pulmonary arteries of adequate size and lack of hemodynamically significant aortopulmonary collaterals, early repair constituted usual management. Some children underwent repair at >3 months of age when diagnosis or referral was delayed or for other logistical reasons. Cardiac catheterization was applied occasionally to clarify coronary anatomy, to better define pulmonary artery anatomy, or to identify aortopulmonary collaterals. Patients identified with nonconfluent pulmonary arteries, absent pulmonary valve syndrome, associated AV canal defect, or significant aortopulmonary collaterals are not included in this review.
There were 55 boys and 44 girls, with an average age at operation of
32.9±26.7 days (median, 27 days; range, 2 to 87 days; Table
).
Fifty-nine were prostaglandin E dependent. Fifty-seven of
these children underwent repair in the neonatal period, and 91% were
considered symptomatic on the basis of cyanosis with or
without hypercyanotic "spells." Of the 42 patients repaired between
31 to 87 days of age, 76% were symptomatic.
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The surgical technique has been reported previously.7 Operative management used deep hypothermia (18°C to 25°C) with either low-flow cardiopulmonary bypass or circulatory arrest. The use of circulatory arrest was reduced in later years as the advantages of low-flow cardiopulmonary bypass became apparent.8 Repair included transannular patch (61 TOF/PS, 9 TOF/PA), homograft reconstruction (5 TOF/PS, 17 TOF/PA), or infundibular patch (7 TOF/PS). The ventricular septal defect was closed through a right ventriculotomy in 96% of the patients (96 of 99). Median length of follow-up was 4 years (range, 1 to 8.8 years).
Statistical Analysis
A multivariate analysis of the following
risk factors for death was undertaken: age at operation, birth and
operative weights, body surface area, pulmonary artery Z
scores, duration of circulatory arrest, myocardial ischemic
time, postoperative arrhythmias, and time to extubation. Time
in the intensive care unit and hospital, reoperation, and the need for
subsequent cardiac catheterization with
pulmonary artery or conduit dilatation or stenting were
reviewed. Inotropic requirements at 24 hours were converted to
inotropic equivalents for purposes of comparison.9 Data
are expressed as mean±SD or median (range). The Kaplan-Meier method
was used to estimate probabilities of survival,
catheterization, and reoperation.
Univariate and multivariate
analyses were performed by use of the Cox proportional-hazards
model for survival and catheterization. A value of
P<0.05 was considered statistically significant.
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Results |
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Hospital Mortality
There were 3 hospital deaths (3%, 3 of 99), all within 30 days of operation. One patient (TOF/PA) died of an apparent arrhythmia after a pulmonary artery line was removed, 1 (TOF/PS) died of right heart failure on postoperative day 6, and 1 (TOF/PS) died on postoperative day 24 of progressive cardiac dysfunction and multisystem organ failure.
Late Mortality
Late mortality (out of hospital and 
31 days after operation)
consisted of 5 late deaths. One patient (TOF/PA) died suddenly 3 months
after operation after routine immunizations, 1 (TOF/PA) died at 3
months with findings of pneumonia at autopsy, 1 (TOF/PA) died at 1 year
from a seizure disorder, 1 (TOF/PA) died at 1 year from uncertain
causes 3 months after right ventricle to pulmonary artery
conduit change, and 1 (TOF/PS) died at 1 year from chronic lung
disease.
Actuarial survival rates were 94% at 1 year and 91.6% at 5 years
(Figure 1). Multivariate
analysis showed diagnosis of TOF/PA and smaller body surface
area to be independent risk factors for death. Not found to be
significant risk factors for mortality were age at surgery (
1 or 1
month of age), sex, weight, pulmonary artery or
pulmonary valve size, circulatory arrest time, cross-clamp
time, cardiopulmonary bypass time, and inotropic
requirements.
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Surgical Morbidity
Eight children had delayed sternal closure 4 to 16 days after
correction. There were no cases of mediastinitis. There were 3
diaphragmatic plications for paralyzed diaphragms and respiratory
impairment 30 to 64 days after operation.
Postoperative arrhythmias occurred in 29 patients (29%), with junctional ectopic tachycardia (JET, 48.3%) and supraventricular tachycardia (17.2%) being the most common diagnoses. There were no deaths directly attributable to these arrhythmias
Catheterization
Twenty-two patients (13 of 73 TOF/PS, 9 of 26 TOF/PA) required
subsequent intervention with cardiac catheterization
and pulmonary artery or homograft conduit dilatation or
stenting. The time to catheter intervention averaged 434 days (median,
288 days; range, 57 to 1570 days), and there were on average 1.9±1.4
(range, 1 to 5) interventions per child. Although
univariate analysis showed diagnosis of TOF/PA,
smaller pulmonary artery Z scores, and age >1 month were risk
factors for catheter intervention, these became statistically
insignificant in multivariate analysis. Freedom
from catheter intervention was 86% at 1 year and 73% at 5 years
(Figure 2).
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Reoperations
Excluding chest closures, there were 25 reoperations in 22
children between 1 month and 5 years 10 months. Fifteen children
undergoing repair in the neonatal period required reoperation, as did 7
children repaired in early infancy (P=NS). Among all
patients (TOF/PS and TOF/PA), freedom from reoperation for any cause
was 90% at 1 year, 83% at 2 years, and 72% at 5 years (Figure 3). However, repair of TOF/PA usually
requires homograft placement to reconstitute right ventricle to
pulmonary artery continuity. These homografts are expected to
require reoperation because the child inevitably outgrows them.
Although freedom from reoperation is analyzed as a function of
diagnosis, ie, TOF/PS versus TOF/PA, the 1-, 2-, and 5-year freedom
from reoperation was 94%, 88%, and 81% for TOF/PS but only 79%,
69%, and 50% for TOF/PA (P=0.01, Figure 4).
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Morbidity directly ascribed to the TOF repair included 3 presumed phrenic nerve injuries necessitating diaphragmatic plication between 30 to 60 days after operation and a single pacemaker at 2 months for heart block. Nine TOF/PA children required 11 reoperations for replacement of right ventricular to pulmonary artery homografts (9 and 10 months and 1, 1.5, 2, 2.5, 3, 4, 4.25, 4.5, and 5 years).
Four patients (2 TOF/PS, 2 TOF/PA) required extension of the right ventricular outflow tract (RVOT) patch, 2 required some form of pulmonary enlargement (1 TOF/PS, 1 TOF/PA), 2 (TOF/PS) required reoperation for progressive muscular RVOT obstruction, and 2 (TOF/PS) had late atrial septal defect closures.
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Discussion |
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Although the first successful TOF repair was accomplished >40 years ago, surgical controversies remain. Foremost among these is the timing of repair. Traditional practice has incorporated a 2-stage repair, consisting of early arteriopulmonary shunting, followed by later repair.10 11 12 As a result of advances in neonatology, anesthesia, and surgery, this "later" repair has come progressively earlier in life. The successful repair early in life by Barratt-Boyes et al13 and Castaneda et al14 in the 1970s has led to the adoption of primary complete TOF repair as a neonate or infant at some centers.
Late complications (including sudden death) have been recognized after 2-stage TOF repair and may be related to time-dependent events occurring before repair that permanently damage the myocardium. Several investigators have suggested that these pathological changes lead to permanent heart damage and have found a lower incidence of ventricular arrhythmias among children repaired at younger ages.4 5 6 7 8 9 10 11 12 13 14 15 16 17 Furthermore, Sullivan et al18 and Hegerty et al19 have shown a relationship between age at repair and an abnormal accumulation of fibrous tissue thought to contribute to right ventricular dysfunction.
It is important to emphasize that these changes appear to be time dependent, resulting from the anatomic substrate that defines TOF. Castaneda et al20 have suggested that 1 of these defining features, right ventricular hypertrophy, results from RVOT obstruction that increases with time. This hypertrophy then often requires surgical resection, establishing a potential substrate for the genesis of ventricular arrhythmias. Supporting these authors’ contentions, Murphy et al 21 has found mortality to be related to older age at operation.
In addition to direct myocardial effects, others have suggested that early repair minimizes secondary damage to other organs, primarily the brain, resulting from chronic hypoxia.1 2 5 Thus, the impetus for earlier repair is a natural extension of these concerns, as well as the recognition that neonatal surgery can be performed with acceptable mortality and morbidity.
Since 1988, 99 children have undergone early TOF repair (<3 months of age) at Boston Children’s Hospital with a hospital mortality of 3%. This mortality is consistent with other corrective neonatal cardiac procedures (ie, arterial switch operation and interrupted aortic arch) and is comparable to mortality documented in older children undergoing 2-stage TOF repair.17 22 23 Because the in-hospital mortality was a low 3% (3 of 99), no statistical inferences could be drawn. Among late deaths, 2 resulted from lung disease and 1 from a seizure, demonstrating that these children can be burdened with noncardiac comorbidities.
Despite low hospital mortality, postoperative arrhythmias did
occur in 29% of our patients. The development of arrhythmias
(predominately JET and supraventricular
tachycardia) was unrelated to age at operation but was
associated with the level of inotropic support required at 24 hours
(the Table
). Although our incidence of JET (14 of
99) is higher than that reported elsewhere, awareness of JET in the
postoperative period has increased, and retrospective reports may
underestimate the incidence.24 25 Nevertheless, our data
suggest that arrhythmias in the postoperative period should be
anticipated. This is particularly important because early recognition
and prompt, aggressive treatment are necessary to minimize morbidity
and mortality.
Our approach represents a significant departure from the
standard 2-stage repair consisting of arteriopulmonary shunting
followed by later repair, and our results must be evaluated in relation
to those obtained with the 2-stage repair. Vobecky et al26
described their experience with 141 children undergoing palliative
modified Blalock-Taussig shunt before repair. In their series, initial
palliation failed in 26% (36 of 141), with 2 deaths at palliation and
7 after palliation but before repair (including 1 after subsequent
palliation). Twenty-six required subsequent operation for palliation
for inadequate palliation, with 2 deaths. Of the remaining 24, 20
underwent repair, with 10 requiring pulmonary arterioplasty.
The 5-year actuarial survival rate was 
90% for these children.
These results demonstrate the exacting nature of early palliative
shunting and that distortion of the right pulmonary artery can
be a significant complication. Beyond the anatomic complications of
shunt placement, the undesirable effects of the shunt-imposed volume
load on the myocardium need to be considered. These results
show that there is a price to pay, with significant mortality, for
shunting before repair. These combined considerations support an
inherent attraction and rationale for avoiding palliative shunting by
proceeding directly to repair early in life. Likewise, data
presented with respect to mortality and reoperation in early
repair must be viewed from this perspective.
In an attempt to minimize late complications of TOF repair, some groups have attempted to limit or avoid the right ventriculotomy. Karl et al27 reported an experience of 366 patients undergoing transatrial, transpulmonary TOF repair between 1980 and 1991. Although the number of symptomatic children included is unclear, only 135 (37%) had undergone some form of previous palliation.
Karl et al27 concluded from their results that the transatrial, transpulmonary TOF repair resulted in a similar operative risk compared with transventricular TOF repair, with a 97.5% actuarial survival rate at 42 months. Although closure of the ventricular septal defect was accomplished through the atrium in all cases, the pulmonary annulus was breached with a transannular patch in roughly half of these patients. The transannular incision, when necessary, was extended onto the infundibulum between 5 and 10 mm. The impact of a right ventriculotomy on late outcome is unclear, but our early results suggest that the intracardiac repair can be safely accomplished via this approach.
Our results are comparable to the few published series of early TOF repair, with the advantage of longer follow-up (median follow-up, 4 years). Hennin et al28 reported a 5-year survival rate of 93% among 30 neonates undergoing repair (median follow-up, 24 months). Groh et al29 reported their experience with 58 slightly older children (median age, 6 months; mean weight, 6 kg) undergoing repair. They reported a 4-year survival rate of 94% and an 88% freedom from reoperation at 4 years.
Whereas all these studies demonstrate that early repair can be accomplished with acceptable mortality, the need for reoperation among some of these patients must be acknowledged. However, the need for reoperation appears to be largely dictated by the anatomic substrate, ie, PS versus PA, and is inevitable in those patients requiring a homograft to restore right ventricle to pulmonary artery continuity. This recognition explains the significantly lower freedom from reoperation for children undergoing repair of TOF/PA. This should be appreciated, as interpretation of the data of Groh et al29 may lead one to conclude that freedom from reoperation decreases with age at repair. Although they reported an 88% freedom from reoperation at 4 years, only 5 of 58 patients underwent repair of TOF/PA.
Subset analysis of our data supports the contention that diagnosis rather than age at repair exerts a greater influence on the need for reoperation. Of the 22 children requiring reoperation, 15 underwent repair as neonates (1557 [26%] neonates versus 7 of 42 [17%] infants 31 to 90 days of age; P=NS). Of the 26 patients undergoing repair of TOF/PA, 10 (38%) have required reoperation, whereas only 12 of 73 requiring TOF/PS repair (16%) have required reoperation. Thus, these reports and our experience would suggest that it is not earlier repair but rather the diagnosis of TOF/PA and the need for homograft insertion that are likely to result in reoperation.
We have demonstrated that early TOF repair can be accomplished with a low mortality, and it is fair to say that the hope expressed by DiDonato et al6 that "safe elective repair in early infancy" of TOF has been realized. Although repair can be performed with acceptable mortality, further efforts need to be directed at defining and minimizing the need for reoperation. Longer follow-up of morbidity and mortality, with particular emphasis on arrhythmias and right ventricular function, is required to define the long-term benefits of early repair.
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Acknowledgments |
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We wish to acknowledge Gary Piercey for his assistance with the statistical analysis.
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Footnotes |
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Reprint requests to Richard A. Jonas, MD, Department of Cardiac Surgery, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115.
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References |
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