ARTICLE IN PRESS

doi:10.1510/icvts.2008.180083

Interactive CardioVascular and Thoracic Surgery 7 (2008) 698–701

www.icvts.org

Best evidence topic - Congenital

Is early primary repair for correction of tetralogy of Fallot
comparable to surgery after 6 months of age?
Hunaid A. Vohra, Louise Adamson, Marcus P. Haw*
Department of Cardiothoracic Surgery, Southampton General Hospital, Southampton, UK

Received 18 March 2008; received in revised form 10 April 2008; accepted 23 April 2008

Summary

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether early
primary repair for correction of tetralogy of Fallot (TOF) resulted in better outcomes than surgery after 6 months of age. Altogether 650
relevant papers were identified using the below mentioned search, eight papers represented the best evidence to answer the specific
question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study
weaknesses were tabulated. We conclude that early primary repair of TOF has been shown to be comparable to later repair, with several
retrospective series concluding that there is no increase in mortality with children under 6 months of age. Freedom from reintervention
has also been shown to be similar irrespective of the age primary repair is undertaken. However, it has been observed that length of
intensive care unit stay, period of mechanical ventilation and the need for inotropes is increased in patients undergoing primary repair at
-3 months of age.
䊚 2008 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

Keywords: Tetralogy of Fallot; Cardiac surgery; Infants; Evidence based medicine

1. Introduction 4. Search strategy

A best evidence topic was constructed according to a
structured protocol. This protocol is fully described in the
ICVTS w1x.
2. Clinical scenario
A 6-week-old male infant is referred to your clinic by the
paediatric cardiologists. He first presented with cyanosis
and was found to have severe right ventricular outflow
tract obstruction (RVOT) with pulmonary stenosis and a
large ventricular septal defect (VSD) on investigations. The
cardiologist has just attended a national conference and
heard about the practice of one stage repair of tetralogy
of Fallot (TOF) in neonates as an alternative to a palliative
procedure followed by a later repair. He asks you whether
you think this case might be suitable for early primary
repair. You discuss it with your consultant who asks you to
review the literature.
3. Three-part question
In wpatients with TOFx is wearly primary repairx comparable
to surgery after 6 months of age in wterms of outcomex?
*Corresponding author. Department of Paediatric Cardiac Surgery, Wessex
Cardiothoracic Centre, Southampton University Hospitals NHS Trust, South-
ampton General Hospital, Tremona Road, Southampton, UK. Tel.: q44-2380
777222; fax: q44-2380798508.
E-mail address: marcus.haw@suht.nhs.uk (M.P. Haw).
䊚 2008 Published by European Association for Cardio-Thoracic Surgery
Medline 1950 to March 2008 using the OVID interface.
wexp ‘Tetralogy of Fallot’yor fallot.tix AND wexp infantyOR
neonat$.mp OR exp Infant, Newborny x and wrepair.mp or
correction.mpx.
5. Search outcome
A total of 650 relevant papers were found from which
eight papers were selected as representing the best
evidence on this topic (Table 1).
6. Comments
Eight clinical studies were found in 1720 patients. The
studies reviewed the operative outcomes in patients under-
going surgery for correction of TOF and investigated wheth-
er age at time of primary repair affected outcome.
In a retrospective study by Ooi et al. w2x, 52 operations
were performed on children under 12 months of age for
repair of isolated TOF. It was shown that age under 3
months at the time of correction of TOF increased the
duration of post-operative ventilation, intensive care unit
(ICU) stay and hospital stay, although it did not affect the
incidence of post-operative morbidity. The authors conclud-
ed that early definitive repair of TOF can be performed
safely in those under 6 months old, and that age at surgery
does not appear to affect the medium term haemodynamic
outcome. They suggest that repair in asymptomatic
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Table 1
Best evidence papers
Author Patient group
Ooi et al., (2006), 52 operations on children under
Eur J Cardiothorac 12 months of age undergoing
Surg, UK w2x correction of isolated TOF
Cohort study (level 2b)
Kolcz and Pizarro, (2005), Two groups of 66 consecutive
Eur J Cardiothorac patients with TOF and
Surg, USA w3x confluent pulmonary arteries
undergoing repair immediately
Cohort study (level 2b) after diagnosis
Group I (ns46) had a median
age of 5 days
Group II (ns20) had a median
age of 56 days
Sousa Uva et al., 56 patients with TOF operated
(1994), J Thorac on at -6 months of age
Cardiovasc Surg,
France w4x 41 patients underwent primary
repair
Cohort study (level 2b)
15 patients underwent initial
palliation
Lee et al., (2006), 240 patients undergoing one
J Cardiovasc Surg stage repair of TOF
(Torino), South Korea
w5x Group 1 – early repair (under
6 months)
Cohort study (level 2b)
Group 2 – late repair (over
6 months)
van Dongen et al., 78 patients -19 months of age
(2003), J Thorac who underwent complete repair
Cardiovasc Surg, of TOF in a 3 year period
Canada w6x
Cohort study (level 2b)
Outcome Key results
Duration of post- Patients under 3 months
operative ventilation old required greater duration
(3.8"1.2 vs. 1.4"0.2 days;
P-0.05)
Duration of ITU stay Those under 3 months old
had longer ITU stay (11"4.1
vs. 5.1"0.8 days; P-0.05)
Duration of hospital Hospital stay was longer in
stay patients under 3 months old
(24.8"8.9 vs. 14.9"1.3 days)
Nakata index A significant increase in Nakata
index was observed only among
neonates (98.54"44.6 vs.
159.60"55.3; P-0.001)
Freedom from At 1 month, 1 and 5 years was
reintervention 100%, 84.2% and 81% in group
I and 100%, 84% and 78.9%
in group II (Ps0.88)
By multivariate analysis,
preoperative weight (2.71"0.38
vs. 3.62"1.04 kg; Ps0.02) and
low arterial saturation in the
early post op period
(86.20"4.8 vs. 94.46"8.2;
Ps0.04) were associated with
the need for reintervention
during follow-up
Mortality One death after initial palliation
(6.7%) and one death after
primary repair (2.4%) (Ps0.47)
Requirement for 56% of patients undergoing
transannular patch primary repair required a
transannular patch vs. 13%
for patients having initial
palliation
Method of RVOT Transannular patch 69% in
reconstruction group 1 vs. 57% in group
(transannular vs. 2; Ps0.21. Branch pulmonary
non-transannular) artery angioplasty 50%
in group 1 vs. 40% in group 2;
Ps0.29
Requirement for Early repair group had more
transventricular transventricular VSD closure
VSD closure than late repair group (46% vs.
22%, P-0.05)
Duration of inotropic Longer in the early repair group
support (114.3"93.4 h vs. 66.2"49.9 h;
P-0.05)
Duration of ICU Longer in early repair group
stay (7.7"13.2 days vs. 4.7"6.7
days; P-0.05)
Use of vasoactive Increased in patients -3 months
drugs of age (ns8; 66%) vs. ns10;
15%: P-0.0001)
Postoperative fluid Higher in those -3 months
requirement (7.2"3.3 vs. 4.7"2.9 mlykgyh;
Ps0.002)
699
Comments
Authors concluded that early
definitive repair of TOF can
be performed safely in those
under 6 months old, and that
age at surgery does not
appear to affect the medium
term haemodynamic
outcome. They suggest that
repair in asymptomatic
patients can be delayed until
3–6 months of age
Authors conclude that
neonatal repair affords a
freedom from reintervention
no different from patients
repaired during infancy
Early primary repair of
symptomatic tetralogy of
Fallot was achieved with a
low mortality rate and is the
authors’ preferred protocol.
They state that initial
palliation remains indicated
in the case of associated cardiac
anomaly, very low weight or
severely hypoplastic
pulmonary tree
All survivors are currently
asymptomatic. Authors
conclude that one stage repair
of TOF can be performed
with low mortality and
morbidity, and that early one
stage repair in the
symptomatic infant can be
performed with low risk,
eliminating the need for
palliative procedures
No operative mortality in
this study, although one
late death occurred. The
authors conclude that
primary repair at an early
age has excellent short-term
outcome, and that patients
(Continued on next page)
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Table 1 (Continued)
Author Patient group Outcome Key results Comments

-3 months of age have

Organ dysfunction Higher incidence of organ increased but transient
dysfunction in patients under intensive care morbidity
3 months. Four organs affected,
ns4; 33% vs. ns1; 1.5%:
P-0.001)

Duration of Longer in patients under

ventilator support 3 months (median 100 h
vs. 18 h; P-0.0001)

Duration of ICU Longer in patients under

stay 3 months (median 5.5 days
vs. 2 days; P-0.002)

Cobanoglu and Schultz, 63 consecutive patients less Mortality Overall mortality 6%. Age Mortality was increased by
(2002), Ann Thorac than 1 year of age undergoing -3 months and weight -6 kg factors, such as aortic cross-
Surg, USA w7x total correction of TOF were not predictors of clamp time more than 60 min
mortality (Ps0.023), cardiopulmonary
Cohort study (level 2b) bypass time more than
90 min (Ps0.016) and
frequent preoperative
respiratory tract infections
(Ps0.008)

Mulder et al., (2002), 938 patients from 12 Mortality In patients F3 months the Marked interinstitutional
Paed Cardiol, USA institutions who underwent overall in hospital mortality variability. Institutional
w8x their initial operation (shunt or was significantly higher than preference may be a
repair) that for older patients for both significant factor in
Cohort study (level 2b) shunts and repairs influencing the choice of
initial surgical procedure
Predictors of initial Age, weight, date of surgery,
surgical management and the interactions between
date of surgery and institutional
volume and between age and
institutional volume were
significant predictors of the
initial surgical management
of TOF

Van Arsdell et al., 227 consecutive children who
(2000), Circulation, had repair of isolated tetralogy
Canada w9x of Fallot from Jan 1993 to June
1998 after change of approach
Cohort study (level 2b) from initial palliation in the
infant to primary repair around
age 6 months or earlier
Median age of repair Fell from 17 to 8 months The best survival and
(P-0.01) physiological outcomes were
achieved with primary repair
Presence of palliative Decreased from 38% to 0% in children aged 3–11
shunt at time of (P-0.01) months
repair
Mortality No mortality with repair at 6
months. Six deaths in patients
with repair after 12 months

Physiological Multivariate analysis showed

outcomes that age -3 months was
independently associated with
prolonged lactate clearance,
ventilation hours and
length of stay (P-0.03)

patients can be delayed until 3–6 months of age. Kolcz and
Pizarro w3x reviewed 66 children under the age of 3 months
with TOF and confluent pulmonary arteries with respect to
mortality, Nakata index and freedom from reintervention
at follow-up. They found that a significant increase in
Nakata index occurred only in neonates and that neonatal
repair afforded a freedom from reintervention no different
from patients repaired in infancy. In a cohort of 56 patients
with TOF operated on at -6 months, Sousa Uva et al. w4x
demonstrated that early primary repair as an alternative
to early palliation followed by later repair was achieved
with a low mortality rate. Lee et al. w5x reviewed the
outcome after one stage repair of TOF in cohort of 240
patients. They studied differences in method of RVOT
reconstruction and closure of VSD as well as duration of
inotropic support and ICU stay in two groups of patients.
Concomitant transventricular VSD closures were performed
more commonly in the early repair group (-6 months) and
similar RVOT reconstruction methods were employed in
both groups. Although, the duration of inotropic support
 ARTICLE IN PRESS
H.A. Vohra et al. / Interactive CardioVascular and Thoracic Surgery 7 (2008) 698–701
and ICU stay was significantly longer in the early repair
group, all survivors were asymptomatic at last follow-up.
These results were similar to those reported by Ooi et al.
w2x. In a similar retrospective review, van Dongen et al. w6x
found that age -3 months was associated with increased
use of vasoactive drugs, higher postoperative fluid require-
ment, higher incidence of organ dysfunction and longer
duration of both ventilator support and ICU stay. They
concluded that primary repair at an early age has excellent
short-term outcome, although patients -3 months of age
have an increased but transient intensive care morbidity.
Cobanoglu and Schultz w7x retrospectively reviewed post-
operative outcomes in 63 patients undergoing total correc-
tion of TOF at -1 year of age. They demonstrated that
factors such as long aortic cross-clamp and cardiopulmonary
bypass time as well as frequent preoperative respiratory
tract infections affected operative survival, but that age
under 3 months and weight -6 kg did not. In a multi-
centre retrospective analysis w8x, which included 938
patients who underwent surgery for TOF in 12 United States
institutions, it was shown that in patients F3 months, the
overall in-hospital mortality was significantly higher than
that for older patients for both shunts and repairs. Multiple
logistic regression analysis indicated that apart from age,
weight, date of surgery and the interactions between date
of surgery and institutional volume, the interaction
between age and institutional volume was a significant
predictor of the initial surgical management of TOF. How-
ever, there was significant inter-institutional variability. In
another study from Toronto w9x, the authors showed that
after change of approach from initial palliation in the
infant with TOF to primary repair around 6 months or
earlier, if clinically indicated (227 consecutive patients),
the mortality improved with time. The deaths reported
were only in patients with primary repair after 12 months
of age. The best survival and physiological outcomes were
achieved with primary repair in children aged 3–11 months,
with multivariate analysis showing that period of lactate
clearance, ventilation and hospital stay being independent-
ly associated with initial repair before -3 months of age.
7. Clinical bottom line
Early primary repair of TOF is comparable to later repair,
with several retrospective reviews concluding that there is
no increase in mortality and re-intervention in infants
-6 months of age. However, it has been consistently shown
that the length of ICU stay, requirement for ventilation and
the need for inotropes is increased in patients undergoing
primary repair at -3 months of age.
References
w1x Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based
medicine in cardiothoracic surgery: best BETS. Interact Cardiovasc
Thorac Surg 2003;2:405–409.
w2x Ooi A, Moorjani N, Baliulis G, Keeton BR, Salmon AP, Monro JL, Haw
MP. Medium term outcome for infant repair in tetralogy of Fallot:
701
indicators for timing of surgery. Eur J Cardiothorac Surg 2006;30:917–
922.
w3 x Kolcz J, Pizarro C. Neonatal repair of tetralogy of Fallot results in
improved pulmonary artery development without increased need for
reintervention. Eur J Cardiothorac Surg 2005;28:394–399.
w4 x Sousa Uva M, Lacour-Gayet F, Komiya T, Serraf A, Bruniaux J, Touchot
A, Roux D, Petit J, Planché C. Surgery for tetralogy of Fallot at less
than six months of age. J Thorac Cardiovasc Surg 1994;107:1291–1300.
w5 x Lee C, Lee CN, Kim SC, Lim C, Chang YH, Kang CH, Jo WM, Kim WH.
Outcome after one-stage repair of tetralogy of Fallot. J Cardiovasc
Surg (Torino) 2006;47:65–70.
w6 x van Dongen EI, Glansdorp AG, Mildner RJ, McCrindle BW, Sakopoulos
AG, Van Arsdell G, Williams WG, Bohn D. The influence of perioperative
factors on outcomes in children aged less than 18 months after repair
of tetralogy of Fallot. J Thorac Cardiovasc Surg 2003;126:703–710.
w7 x 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.
w8 x Mulder TJ, Pyles LA, Stolfi A, Pickoff AS, Moller JH. A multicenter
analysis of the choice of initial surgical procedure in tetralogy of Fallot.
Pediatr Cardiol 2002;23:580–586.
w9 x Van Arsdell GS, Maharaj GS, Tom J, Rao VK, Coles JG, Freedom RM,
Williams WG, McCrindle BW. What is the optimal age for repair of
tetralogy of Fallot? Circulation 2000;102(19 Suppl 3):III123–129.
eComment: Correction of tetralogy of Fallot
Author: Theodor Tirilomis, Department for Thoracic, Cardiac, and Vas-
cular Surgery, University of Göttingen, Göttingen 37075, Germany
doi:10.1510/icvts.2008.180083A
I read with great interest the best evidence article by Vohra et al. w1x
regarding optimal timing for repair of tetralogy of Fallot. The authors
searched relevant papers to answer the question if early primary repair is
comparable to surgery after 6 months of age.
Reading the title of the topic two questions arise; first, what is early
repair and second, if we are talking about early repair what should the
definition of late repair be? Should early repair be related to the time of
diagnosis confirmation or to the age of the patient? In presented publications
patient groups vary widely regarding age, from newborn age w2x, 6 months
w3x, 12 months w4x, to older patients w5x. Should late repair be performed
after the first year of life or after 6 months or should indication for
corrective surgery be body weight related?
Data of this best evidence topic w1x clearly demonstrate that repair of
tetralogy of Fallot can be performed safely at any age, but mortality and
especially morbidity are, even if low, increased in infants under three
months of age. In accordance to these findings in symptomatic patients
younger than three months we have to discuss every individual case carefully
and sometimes even the alternative procedure of two-step repair should be
taken into account.
References
w1x Vohra HA, Adamson L, Haw MP. Is early primary repair for correction
of tetralogy of Fallot comparable to surgery after 6 months of age?
Interact Cardiovasc Thorac Surg 2008;7:698–701.
w2x Kolcz J, Pizzaro C. Neonatal repair of tetralogy of Fallot results in
improved pulmonary artery development without increased need for
intervention. Eur J Cardiothorac Surg 2005;28:394–399.
w3x Lee C, Lee CN, Kim SC, Lim C, Chang YH, Kang CH, Jo WM, Kim WH.
Outcome after one-stage repair of tetralogy of Fallot. J Cardiovasc
Surg (Torino) 2006;47:65–70.
w4x Ooi A, Moorjani N, Baliulis G, Keeton BR, Salmon AP, Monro JL, Haw
MP. Medium term outcome for infant repair in tetralogy of Fallot:
indicators for timing of surgery. Eur J Cardiothorac Surg 2006;30:917–
922.
w5x van Dongen EI, Glansdorp AG, Mildner RJ, McCrindle BW, Sakopoulos
AG, van Arsdell G, Williams WG, Bohn D. The influence of perioperative
factors on outcome in children aged less than 18 months after repair
of tetralogy of Fallot. J Thorac Cardiovasc Surg 2003;126:703–710.