Surgical outcomes for patients with pulmonary atresia/major
aortopulmonary collaterals and Alagille syndrome†
Richard D. Mainwaringa,*, Ahmad Y. Sheikha, Rajesh Punnb, Vadiyala Mohan Reddyaand Frank L. Hanleya
aDivision of Pediatric Cardiac Surgery, Lucile Packard Children’s Hospital/Stanford University School of Medicine, Stanford, CA, USA
bDivision of Pediatric Cardiology, Lucile Packard Children’s Hospital/Stanford University School of Medicine, Stanford, CA, USA
* Corresponding author: Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRC, Stanford, CA 94305, USA. Tel: +1-650-723-0190;
fax: +1-650-723-0707; e-mail: firstname.lastname@example.org (R.D. Mainwaring).
Received 2 September 2011; received in revised form 26 October 2011; accepted 3 November 2011
OBJECTIVES: Pulmonary atresia with major aortopulmonary collateral arteries (PA/MAPCAs) is a complex congenital heart defect that
has undergone significant advances in treatment over the past 15 years. A small subset of patients with PA/MAPCAs have associated
Alagille syndrome, which can have an adverse impact on many other organ systems. The purpose of this study was to review our insti-
tutional outcomes for the surgical patients with PA/MAPCAs and Alagille syndrome.
METHODS: This was a retrospective review of patients with PA/MAPCA’s and Alagille who underwent surgical reconstruction from
November 2001 to August 2011. Fifteen patients were identified in our data base. Thirteen had pulmonary atresia with ventricular
septal defect (PA/VSD) and two had pulmonary atresia with intact ventricular septum (PA-IVS).
RESULTS: There has been no early or late mortality in this cohort of 15 patients with PA/MAPCA’ and Alagille syndrome. The patients
have undergone a total of 38 cardiac surgical procedures. Ten of the 13 patients with PA/VSD have achieved complete repair, including
unifocalization, a right ventricle to pulmonary artery conduit and closure of all intra-cardiac shunts. The three unrepaired patients with
PA/VSD remain potential candidates for eventual complete repair, while the two patients with PA-IVS remain viable candidates for a
single ventricle pathway. The patients in this series have also undergone 12 major non-cardiac procedures.
CONCLUSIONS: The data demonstrate that surgical reconstruction of PA/MAPCAs can be successfully achieved in patients with Alagille
syndrome. The longer-term prognosis remains guarded on the basis of the multi-organ system involvement of Alagille syndrome.
Keywords: Congenital heart disease • Liver • Pulmonary arteries/veins • Pulmonary vascular resistance/hypertension
Pulmonary atresia with major aortopulmonary collateral arteries
(PA/MAPCA’s) is a relatively rare form of congenital heart defect.
Advances in the surgical treatment of PA/MAPCA’s over the past 15
years have led to improved outcomes for these patients [1–4].
However, a significant number of patients with PA/MAPCA’s have
associated chromosomal syndromes. The most frequently cited
genetic defects identified with PA/MAPCA’s include chromosome
22q11 deletion and Alagille syndrome. The presence of genetic syn-
dromes has been shown to adversely affect outcomes for a wide
range of congenital heart defects . This principle is particularly
applicable in more complex defects, and poorer outcomes have
been documented separately for correction of tetralogy of Fallot 
and pulmonary atresia . Given the complexity of treatment
required for PA/MAPCA’s, it is anticipated that outcomes would be
significantly influenced by these chromosomal syndromes.
Alagille syndrome is a dominantly inherited disorder linked to
mutations of the JAG1 gene . This disorder affects multiple
organ systems, including the heart, liver, kidneys, vasculature,
skeleton, eyes and face. More than 90% of patients with Alagille
syndrome have congenital heart defects, with the majority of
these involving the right-sided cardiac structures . The sine
qua non of Alagille syndrome from a cardiac standpoint is
branch pulmonary artery stenosis. However, a small subset of
patients with Alagille syndrome will have tetralogy of Fallot
(10–15%) or tetralogy of Fallot with pulmonary atresia (5%) .
The incidence of PA/MAPCA’s in association with Alagille syn-
drome has not been well documented to date.
The purpose of this study was to review our institutional ex-
perience in the surgical management of PA/MAPCA’s and
Alagille syndrome. It is our goal that this may reveal important
principles regarding the combination of a complex congenital
heart defect and genetic disorder.
MATERIALS AND METHODS
This study was approved by the Institutional Review Board (IRB)
at Stanford University. Medical records were reviewed and a
†Presented at the 25th Annual Meeting of the European Association for
Cardio-Thoracic Surgery, Lisbon, Portugal, 1–5 October, 2011.
© The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
European Journal of Cardio-Thoracic Surgery 42 (2012) 235–241
doi:10.1093/ejcts/ezr310Advance Access publication 7 March 2012
an intraoperative flow study, there were very few patients who were able to
go on to the single-stage complete repair. So physiologically it seems as if
there is some difference.
Dr Carotti: Moving from the association with Alagille syndrome and focus-
ing on the intraoperative pulmonary artery flow study, the authors report dif-
ferent parameters compared to those that they have historically and at least
initially used. This is a flow rate of 3 l/min/m2and a mean pulmonary arterial
pressure cut-off value of 25 mmHg.
Our own experience based strictly on Dr. Hanley’s initial protocol, using a
flow rate of 2.5 l/min/m2with a mean pulmonary arterial pressure cut-off
value of 30 mmHg showed a 94% accuracy of the test in predicting the possi-
bility of simultaneous VSD closure, and a 91% accuracy in predicting the post-
repair mean pulmonary arterial pressure.
My second question: Why did you abandon the original parameters and
how did you develop the new ones?
Dr Mainwaring: It is a good question. The change occurred about a decade
ago, and we increased the threshold. We did not abandon what we were
doing. We increased the threshold because we had a few patients in whom
we closed the VSD, got into the ICU, and then found that they were having
trouble. So we have increased our parameters, as you said, to 3 l/min/m2and
accepting under 25 mmHg of pressure in the pulmonary arteries.
Dr Carotti: And my last question: I noticed that, within the noncardiac pro-
cedures, a tracheal reconstruction is reported. Was it due to a primary lesion
of the trachea, or to a secondary lesion occurring during the unifocalization
Dr Mainwaring: Most of the noncardiac procedures were liver-related, but
there was one patient who, about a year after unifocalization, presented with
tracheal stenosis and underwent tracheal reconstruction.
Dr R.A. Neirotti (Brookline, MA, USA): How many of those patients who
underwent complete two ventricle repair, end up having normal pulmonary
artery pressure in their follow—up?
Dr Mainwaring: We only would have cath data in a small number of those
patients, so I did not pull that data for this study.
Dr Neirotti: I think that is a very important piece of information, both in
this group of patients as well as in those patients without the syndrome in
order to justify such a major operation.
Dr Mainwaring: Your point is well taken. The patients in whom we would
have data would be those patients who are coming back for conduit change
where we would do a cardiac catheterization, so that would have been four
Dr V. Hraska (Sankt Augustin, Germany): I have a very brief question. What
is your policy on genetic counselling of the parents in this specific disease?
The combination of Alagille syndrome with MAPCAs sounds pretty peculiar.
Dr Mainwaring: Yes. That is an excellent question. I thought you were
going to ask me how much we had invested in each patient, which would
probably exceed a million dollars per patient. But right now our public policy
in the United States is to take care of virtually every patient unless there is
something that is so clearly lethal that that would provide a mandate. But
until our public policy changes, we move forward and treat what we can
R.D. Mainwaring et al. / European Journal of Cardio-Thoracic Surgery