(Circulation. 2000;102:III-123.)
© 2000 American Heart Association, Inc.
Surgery for Congenital Heart Disease |
What is the Optimal Age for Repair of Tetralogy of Fallot?
From the Divisions of Cardiac Surgery and Cardiology (R.M.F., B.W.M.), The Hospital for Sick Children, Toronto, and the Departments of Surgery and Pediatrics (R.M.F., B.W.M.), the University of Toronto, Toronto, Canada.
Correspondence to Dr Glen Van Arsdell, Suite 1525, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. E-mail glen.vanarsdell{at}sickkids.on.ca
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Abstract |
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Background—Controversy regarding the timing for the repair of tetralogy of Fallot centers around initial palliation versus primary repair for the symptomatic neonate/young infant and the optimal age for repair of the asymptomatic child. We changed our approach from one of initial palliation in the infant to one of primary repair around the age of 6 months, or earlier if clinically indicated. We examined the effects of this change in protocol and age on outcomes.
Methods and Results—The records of 227 consecutive children who had repair of isolated tetralogy of Fallot from January 1993 to June 1998 were reviewed. The median age of repair by year fell from 17 to 8 months (P<0.01). The presence of a palliative shunt at the time of repair decreased from 38% to 0% (P<0.01). Mortality (6 deaths, 2.6%) improved with time (P=0.02), with no mortality since the change in protocol (late 1995/early 1996). Multivariate analysis for physiological outcomes of time to lactate clearance, ventilation hours, and length of stay, but not death, demonstrated that an age <3 months was independently associated with prolongation of times (P<0.03). Each of the deaths occurred with primary repair at an age >12 months. The best survival and physiological outcomes were achieved with primary repair in children aged 3 to 11 months.
Conclusions—On the basis of mortality and physiological outcomes, the optimal age for elective repair of tetralogy of Fallot is 3 to 11 months of age.
Key Words: tetralogy of Fallot • survival • physiology
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Introduction |
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Opinions regarding the optimal time for the repair of tetralogy of Fallot vary.1 2 3 4 5 Debate continues regarding the use of initial palliation versus primary repair in symptomatic neonates. A debate also exists about the timing of repair for the asymptomatic infant.
For many years, the protocol at the Hospital for Sick Children in
Toronto was to repair children with tetralogy of Fallot at an
age of 
18 months.1 Infants presenting with cyanosis
or spells were initially palliated with a Blalock-Taussig shunt. In the
latter part of 1995 and early 1996, an institutional shift in
protocol was made to perform the primary repair of tetralogy of Fallot
at 6 months of age. Infants who were symptomatic before
that age were repaired primarily.
Data were collected and reviewed for children who were operated on both before and after the change in protocol. We evaluated the changes in patient demographics, operative strategies, and outcomes on the basis of the year of repair. A separate analysis based on age at repair was performed to define the optimal age for repair.
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Methods |
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The Hospital for Sick Children in Toronto, Division of Cardiovascular Surgery computer database was searched for all cases of tetralogy of Fallot between January 1993 and June 1998. Those patients with pulmonary atresia, absent pulmonary valve syndrome, or an atrioventricular septal defect were excluded (those with an atrioventricular septal defect were recently reported).6 Children with other metabolic or genetic disorders were not excluded. We are not aware of any exclusion of children with tetralogy of Fallot from operative therapy. Repair of tetralogy of Fallot, in its isolated form was identified in 227 consecutive children. These children are the subject of this report. Hospital records, clinic records, and computer database echocardiographic reports were reviewed. The data reviewed is listed in Table 1
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Statistical Methods
Data are described as frequencies, medians with ranges, and
means±SD, as appropriate. Where data are missing, the number of
non-missing values is given. Trends over time (by year) were sought
with Mantel-Haenszel 
2, Fisher’s exact test,
and Pearson and Spearman correlation coefficients. Patients were
divided into 3 groups by age of repair. Clinical experience suggested
that outcomes for either morbidity or mortality were less favorable in
the very young and in children >1 year old. For morbidity and
mortality, age at repair was initially tested as a continuous
variable, with significant associations noted. However, this
analysis seemed to oversimplify the relationships with age.
Therefore, we divided the variable age into 3 logical categories.
Thus, we could define more complex associations, particularly
relationships with greater morbidity or mortality at one or both
extremes of age. The 3 groups were compared using
2, ANOVA, and Kruskal Wallis
ANOVA.
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Results |
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Cohort Description
Preoperative Characteristics
There were 130 male children (57%). The median age of repair was 14 months (range, 8 days to 9.6 years), the mean weight was 9.4±4.5 kg (n=226), and the mean body surface area was 0.44±0.12 m2 (n=226). The mean preoperative hemoglobin level was 14.0±2.1 mg/dL (n=208), and the mean preoperative arterial saturation was 85±11% (n=204). Previous procedures were performed in 28% of the children (62 of 222); they included 49 systemic to pulmonary artery shunts, 13 balloon dilations of the pulmonary outflow tract or pulmonary arteries, 1 repair of an aortopulmonary window, and 1 right ventricular outflow patch with pulmonary arterioplasty (some children had >1 procedure). An anterior descending coronary artery crossing the right ventricular outflow tract or an accessory anterior descending coronary artery was identified in 15 patients (7%).
Operative Characteristics
Mean total cardiopulmonary bypass time for repair was
126±44 minutes (n=225), and the mean cross-clamp time was 50±17
minutes (n=225). A transventricular closure of the
ventricular septal defect (transventricular
repair) was performed in 108 patients, and a transatrial closure of the
ventricular septal defect (transatrial repair) was
performed in 112 patients (n=220). In those having a transatrial
repair, 70 (63%) had a small infundibular patch placed as well. A
transannular patch was used in 131 children (59%, n=221), of which 91
had placement of a monocusp valve (n=220). The type of monocusp that
was predominantly used (nearly 70%) is described by Gundry et
al.7
Branch pulmonary arterioplasty was performed in relation to a previous shunt to the pulmonary artery in 16 children (33% of 49 total shunts). In those children having an abnormal anterior descending coronary system (n=15), the repair was performed transatrially in all but 2. Despite the aberrant or accessory anterior descending coronary artery, a transannular patch was placed in 53% of these children (8 of the 15). No conduits were used in association with coronary anomalies (there was 1 death in this subset).
The mean right ventricular systolic pressure after repair was 37±10 mm Hg (n=203), the mean pulmonary artery systolic pressure was 26±10 mm Hg (n=177), and the mean systolic systemic pressure was 76±11 mm Hg (n=197). Central venous pressures measured in the operating room after repair were 10±3 mm Hg (n=142). Modified ultrafiltration after repair was performed in 90% of the children (185 of 205).
Postoperative Characteristics
The median length of stay in the intensive care unit was 4 days
(range, 1 to 103 days; n=211). The median time to extubation was 26
hours (range, 2 hours to 101 days; n=213). Time to normalized serum
lactate ranged from 0 hours to 9 days (median, 6 hours; n=148) after
arrival in the intensive care unit.
Reoperation for residual lesions was performed in 6 children (3%); 2 had residual ventricular septal defects, and the others had right pulmonary arterioplasty, superior vena cava stenosis, atrial septal defect closure, and conversion from a valve sparing procedure to a transannular patch. Junctional ectopic tachycardia was noted in 7% (14 of 214). Death before hospital discharge occurred in 6 children (2.6%). Each of these deaths occurred in a child receiving a transannular patch, and each occurred before the change in protocol in the beginning of 1996. None of the deaths occurred in a child with a previous palliative shunt.
Characteristics and Results by Year of Repair
The median age of repair fell from 17 months in 1993 to 8 months
in 1998 (Figure 1). The number of
children having a previous systemic to pulmonary artery shunt
fell from 38% (n=32) to 0% (n=24) for 1993 and 1998, respectively
(Table 2). Preoperative use of
ß-blockers increased from 18% in 1993 to 42% in 1998 (Table 2). Hospital mortality also significantly decreased between 1993
and 1998 (Figure 2).
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Operative technique changed from primarily a
transventricular approach to transatrial repair (Table 2
). Other trends by year (detailed in Table 2) included a
diminished use of a monocusp transannular patch with later year of
repair and increased use of post-bypass modified ultrafiltration. No
change occurred in the use of a transannular patch over time.
Cardiopulmonary bypass and cross-clamp times increased.
A comparison of median cumulative hospital stays for infants <3 months of age who had a systemic to pulmonary artery shunt followed by later repair and for infants <3 months of age who had primary repair showed a trend toward less total hospital time in the primary repair group. This did not reach significance (shunt and subsequent repair: median, 32 days; range, 21 to 63 days; primary repair: median, 21 days; range, 6 to 112 days; P=0.06).
Physiological Outcomes by Year of
Repair
The median time to a normal lactate level fell from 19 hours to 3
hours between 1993 to 1998 (Table 2). Additionally, the median
time to extubation decreased from 43 to 16 hours. By year of repair, no
change occurred in right ventricular outflow gradient, as
measured by echocardiography at the time of
discharge. No change occurred in the mean postoperative right
ventricular pressure by intraoperative direct catheter or
echocardiographic measurement. The mean right
ventricular to systolic pressure ratio stayed
constant over the 5 years. Details of the above findings are shown in
Table 2.
Results by Age at Repair
To determine the distribution of morbidity and mortality in the
entire database, age at repair was divided into the following 3 groups:
<3 months, 3 to 11 months, and >12 months. These data were
analyzed for outcomes.
Time to serum lactate normalization was least in children <3 months of
age and greatest for those >12 months of age. Details of age-related
data are shown in Table 3. Those children
<3 months of age at repair had substantially more ascites and a
greater use of a peritoneal drain. The median time in the intensive
care unit and median time to extubation were longest for those children
<3 months of age and equivalent for those aged 3 to 11 months and
those aged >12 months (Figure 3).
Hospital deaths were significantly higher in those children >12 months
of age compared with those <3 months and those aged 3 to 11 months
(P=0.02; Figure 4).
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Transannular Patches
Children receiving a transannular patch had a longer median time
to extubation (patch: median, 29 hours; range, 2 hours to 101 days;
n=123; no patch: median, 23 hours; range, 3 hours to 71 days; n=85;
P=0.04) and a longer time to discharge from the intensive
care unit (patch: median, 4 days; range, 1 to 103 days; n=121; no
patch: median, 3 days; range, 1 to 72 days; n=85; P<0.01)
when compared with those who did not have a transannular patch. A
tendency existed toward having a poorer grade of right
ventricular function, as measured by
echocardiography at hospital discharge, if a
transannular patch had been placed (patch: good function, 87; mild
decrease, 15; moderate decrease, 3; poor function, 1; n=106; no patch:
good function, 58; mild decrease, 3; moderate decrease, 1; poor
function, 0; n=62; P=0.06). Transannular patches were
associated with more pulmonary insufficiency, as determined by
echocardiography at discharge (patch: trace
insufficiency, 2; mild, 17; moderate, 15; severe, 43; n=77; no patch:
trace insufficiency, 2; mild, 15; moderate, 15; severe, 15; n=47;
P=0.01); however, a monocusp valve lessened the grade of
insufficiency (median grade insufficiency with a monocusp valve was
mild; range, none to severe; n=50; P=0.01).
Transatrial Versus Transpulmonary Repair
More transatrial repairs were performed in recent years. When
compared with transventricular repairs, transatrial repairs
had longer cross-clamp times (transatrial: median, 56 minutes; range,
27 to 157 minutes; n=111; transventricular: median, 41
minutes; range, 22 to 91 minutes; n=108; P<0.01), a lower
percentage of transannular patching (43% versus 57% in
transventricular repair; both n=108; P=0.01), a
shorter time to extubation (transatrial: median, 21 hours; range, 2
hours to 94 days; n=106; transventricular: median, 33
hours; range, 3 hours to 101 days; n=96; P<0.01), and fewer
days in intensive care (transatrial: median, 3 days; range, 1 to 103
days; n=105; transventricular: median, 4 days; range, 2 to
72 days; n=95; P<0.01). Right ventricular
function at hospital discharge was not different between the 2 groups
(transatrial: good function, 69; mild decrease, 5; moderate decrease,
2; poor function, 1; n=77; transventricular: good function,
71; mild decrease, 13; moderate decrease, 2; poor function, 0; n=86;
P=0.06).
Independent Factors Associated With Outcomes
The independent factors associated with the outcomes of time to
normal serum lactate level, time to extubation, and time to hospital
discharge were determined with general linear regression modeling.
There were an insufficient number of deaths to include this as an
outcome. Variables tested in the models were preoperative use of
ß-blockers, preoperative oxygen saturation, preoperative hemoglobin,
presence of a palliative shunt, date of operation, age at repair (<3
months, 3 to 11 months, and >12 months), operative cross-clamp and
cardiopulmonary bypass times, transatrial versus
transventricular repair, use of a transannular patch, and
the presence of postoperative junctional ectopic
tachycardia. Age <3 months and earlier year of operation
were independent factors associated with prolonged time to lactate
clearance. Independent factors associated with longer intubation were
age <3 months, higher preoperative hemoglobin, the occurrence of
junctional ectopic tachycardia, and a shorter cross-clamp
time. Independent factors associated with increased total hospital days
were age <3 months, lower preoperative oxygen saturation, junctional
ectopic tachycardia, and the presence of a palliative shunt
at the time of definitive repair. The details of this analysis
are shown in Table 4.
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Discussion |
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One of the problems with analyzing data on the repair of tetralogy of Fallot is that many studies span large periods of time.1 2 4 Therefore, advances in multiple areas of treatment are reflected in the outcomes. The substantial changes in treatment protocol at this institution regarding both the timing of repair and a move to primary repair provide an opportunity to study the effects on outcomes over broad age ranges in a relatively short time frame (5.5 years). This is a unique opportunity to analyze age-related outcomes with a minimal era effect.
Year of Repair
In this cohort, median age of repair decreased with later year of
repair and there were fewer previously present systemic to
pulmonary artery shunts. The use of a transatrial rather than a
transventricular repair increased over time. The shift to
more transatrial repairs was a natural evolution and not a planned
change. Univariate analysis demonstrated an
improvement in physiological outcome measurements
with the use of transatrial repair. When year of repair was controlled
in the multivariate model, transatrial repair was not
an independent factor for improved physiological outcome.
Interestingly, in the multivariate model, a shorter
cross-clamp time was a risk factor for longer intubation time. Shorter
cross-clamp times were associated with earlier year of repair and
transventricular repairs. The increased preoperative use of
ß-blockers in the later years of the study was not a
univariate or independent risk factor for measured
outcomes. In general, ß-blockers were used to stabilize a child for
elective repair. Because we had few deaths, a
multivariate analysis could not be done for
mortality. A significant improvement in survival with later year of
repair and the improvement in physiological
parameter measurements, such as serum arterial
lactate and duration of intubation, over time suggest a better
physiological tolerance of the procedure with the
new protocol.
Age of Repair
When screening the data for tolerance to the procedure, it is
clear that age is important. Most infants who had repairs performed at
<3 months of age were operated on during the later years, when there
was a concerted effort to extubate early. These infants still had
prolonged intubation times when compared with those aged 3 to 11 months
and >12 months. We interpret this as an indicator of greater
physiological stress. In the
multivariate model, age <3 months was an independent
risk factor associated with a prolonged time to normalization of serum
lactate, time to extubation, and length of hospital stay. Nevertheless,
outcomes in this group were good (no mortality; n=17). The caveat to
this finding is that if one makes surgical decisions on the basis of
probabilities, one must accept that with greater numbers, a mortality
difference is possible because of the duration of illness. Mitigation
of this possibility might occur with the development of greater
institutional expertise with increasing cumulative experience.
The lower age limit for better tolerance of repair may be <3 months. However, because the number of patients younger than 3 months of age is small, a meaningful assessment of age at repair of <28 days, 28 to 60 days, and 61 to 90 days is not possible. It could be that the natural physiological change in tolerance is 2 months or some other time. However, the data are clear that very young infants tolerate the procedure less well than older infants.
Although we have changed to primary repair of symptomatic neonates rather than initial palliation followed by repair before 1 year of age, the data from this cohort is insufficient to document if this is the best course of action. Combined hospital and intensive care unit days (a reflector of cumulative cost) for systemic to pulmonary artery shunt followed by later repair was nearly significantly greater (P=0.06) than primary repair alone in a child <3 months. With a few more patients in each arm, this number would likely have achieved significance. Ungerleider et al8 previously outlined this concept in a small cohort.
We abandoned the routine use of a Blalock-Taussig shunt in the symptomatic infant with tetralogy of Fallot because of the previously documented morbidity and interval mortality reported by this institution9 and others.10 11 We did not identify anatomic criteria, such as an anomalous anterior descending coronary artery crossing the right ventricular outflow tract or small pulmonary arteries, in the present cohort that would have precluded primary repair. It is possible that specific contraindications to primary repair exist, such as the comorbidities of cerebral hemorrhage or infection.
Not all reports have shown important problems with neonatal shunts in a biventricular setting.4 Outstanding outcomes have also been achieved by performing a shunt for symptoms in early infancy and following this with complete repair within the next year or so.4 A multi-institutional observational study based on institutional practice (such as those done by the Congenital Heart Surgeons Society) would be helpful to answer this question. Experience at this institution with balloon dilation of the right ventricular outflow tract for symptomatic tetralogy of Fallot in early infancy has not been gratifying because of a failure to reliably relieve cyanosis. We no longer use this approach except under unusual circumstances.
As a group, infants aged 3 to 11 months had the most rapid recovery from operative therapy, as measured by reflectors of physiological tolerance, when compared with those at other ages. No deaths occurred in this age group. We think this indicates the greatest physiological tolerance to repair and, therefore, the optimal age for repair.
The group of children >12 months at the time of repair had the least favorable outcomes (6 deaths in 135 treated; 4.4% mortality; P=0.02). Despite the fact that each of these deaths occurred in a child who did not have a previous shunt, the multivariate model showed previous palliation to be a risk for longer hospitalization. We speculate that the volume-loading provided by the systemic to pulmonary artery shunt protects against the unfavorable right ventricular diastolic stiffness found in some older children but may unfavorably affect systolic function.
Transannular Patch
Patients receiving a transannular patch tolerated the repair less
well. Each of the deaths occurred in a child who received a
transannular patch. In the multivariate model; however,
a transannular patch was not a risk factor for prolonged time to
lactate clearance, extubation, or hospital stay. Preservation of the
pulmonary annulus in tetralogy of Fallot has been reported as
>80% by Yasui et al12 when a concerted effort toward
preservation was made. Improved outcomes without a transannular patch
by univariate analysis and the fact that surgeon
variance seems to exist in the use of a transannular patch suggest that
efforts to preserve the pulmonary annulus and valve are
favorable in the short-term.
Transatrial Transpulmonary Repair Versus
Transventricular Repair
The favorable effects on intensive care and ventilation time seen
in the transatrial repair patients are probably accounted for by the
fact that most of the transatrial repairs occurred in infants aged 3 to
11 months and were performed in more recent years. A suggestion of a
better grade of right ventricular function on the
predischarge echocardiogram existed in the transatrial repair group
(P=0.06). Stellin et al13 and Miura and
colleagues14 had similar findings of
ventricular function with transatrial repair.
Conclusions
Substantial changes in the treatment protocol for tetralogy of
Fallot were made. These changes are characterized by a shift to primary
repair at a younger age and an increasing percentage of transatrial
repairs. Outcomes improved with the change in strategy. By
multivariate analysis, infants <3 months of
age had statistically significant evidence of greater
physiological stress but not mortality. The
unfavorable outcomes seen in this study occurred in children aged >12
months at primary repair. On the basis of reflectors of
physiological tolerance and mortality, the optimal
age for elective repair of tetralogy of Fallot is 3 to 11 months.
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References |
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