Translational Pediatrics Complete

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July2016.Volume5Number3Pages109-184TranslationalPediatrics
ISSN 2224-4336
Vol 5, No 3
July 2016
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TRANSLATIONAL PEDIATRICSTRANSLATIONAL PEDIATRICSTRANSLATIONAL PEDIATRICS
Focus issue on Trends and Innovations in Caring for Patients with Congenital Heart Defects
Guest Editor: Ali Dodge-Khatami, MD, PhD, University of Mississippi Medical Center, USA
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Editor-in-Chief
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Xiangya Hospital of Central South University, China
Deputy Editor-in-Chief
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Western Sydney Genome Diagnostics, Western Sydney Genetic Program, The
Children’s Hospital at Westmead, Sydney, Australia.
Editorial Board
Stuart B. Bauer, MD
Boston, USA
Robert J. Bollo, MD
Salt Lake City, USA
Andrew L. Chang, MD
San Diego, USA
Patrick HY Chung, MBBS
(HK), FRCSEd (Paed), FCSHK,
FHKAM
Hong Kong, China
Amanda Dixon-McIver, BMLSc,
MSc, PhD
Auckland, New Zealand
Ali Dodge-Khatami, MD, PhD,
Professor
Jackson, USA
Ciro Esposito, MD, PhD, MFAS
Naples, Italy
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FRCPC
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East Lansing, United States
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Randwick, Australia
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Groningen, The Netherlands
Haruki Komatsu
Chiba, Japan
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Ann Arbor, USA
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Memphis, USA
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Akron, USA
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Edmonton, Canada
William D. Rhine, MD
Stanford, USA
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Oklahoma City, USA
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Würzburg, Germany
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Nagoya, Japan
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Hanoi, Vietnam
Shawn C. West, MD, MSC
Pittsburgh, USA
Gary Wing Kin Wong, MD,
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Lucille L. Ye

© Translational Pediatrics. All rights reserved. Translational Pediatrics Vol 5, No 3 July 2016
Table of Contents
Editorial
109 Advances and research in congenital heart disease
Ali Dodge-Khatami
112 The battleground of the stenotic branch pulmonary arteries: the surgical approach of “less is more”
Damien P. Kenny, Jonathan McGuinness, Ziyad M. Hijazi
Original Article
114 Antegrade cerebral perfusion at 25 ℃ for arch reconstruction in newborns and children preserves
perioperative cerebral oxygenation and serum creatinine
Bhawna Gupta, Ali Dodge-Khatami, Juan Tucker, Mary B. Taylor, Douglas Maposa, Miguel Urencio, Jorge D. Salazar
125 How to set-up a program of minimally-invasive surgery for congenital heart defects
Juan-Miguel Gil-Jaurena, Ramón Pérez-Caballero, Ana Pita-Fernández, María-Teresa González-López, Jairo Sánchez,
Juan-Carlos De Agustín
Review Article
134 Goal-directed-perfusion in neonatal aortic arch surgery
Robert Anton Cesnjevar, Ariawan Purbojo, Frank Muench, Joerg Juengert, André Rueffer
142 Hypoplastic left heart syndrome: current perspectives
Christopher E. Greenleaf, J. Miguel Urencio, Jorge D. Salazar, Ali Dodge-Khatami
148 Prophylactic arrhythmia surgery in association with congenital heart disease
Constantine Mavroudis, Barbara J. Deal
160 Critical cardiac care in children: looking backward and looking forward
Paul A. Checchia
Case Report
165 Reverse Szabo technique for stenting a single major aorto-pulmonary collateral vessel in pulmonary
atresia with ventricular septal defect
Igor V. Polivenok, John P. Breinholt, Sri O. Rao, Olga V. Buchneva
Pediatric Epilepsy Column (Review Article)
169 Preoperative evaluation and surgical decision-making in pediatric epilepsy surgery
Katrina Ducis, Jian Guan, Michael Karsy, Robert J. Bollo
Pediatric Epilepsy Column (Editorial)
180 Surgical advancements in pediatric epilepsy surgery: from the mysterious to the minimally invasive
Robert J. Bollo
Correspondence
183 Klinefelter syndrome: fertility considerations and gaps in knowledge
Leena Nahata, Richard N. Yu, Laurie E. Cohen

© Translational Pediatrics. All rights reserved. Transl Pediatr 2016;5(3):109-111tp.amegroups.com
The fate of babies born with congenital heart disease
(CHD) has dramatically changed in the last 4–5 decades,
going from a universally fatal condition in the vast
majority of patients in the absence of diagnosis or
intervention, to an entity whose outcome, at least in
terms of peri-operative/hospital stay, has improved to an
expected survival of about 96%. Indeed, since the first
surgical solution for any type of congenital heart defect in
1938, ligation of a patent ductus arteriosus by Dr. Robert
Gross at Boston Children’s Hospital (1), followed by the
pioneering work of Alfred Blalock and Helen Taussig in
the palliation of “blue babies” with tetralogy of Fallot
in 1944 (2), to the critical breakthrough of open heart
surgery with inflow occlusion and repair of an atrial
septal defect by F. John Lewis in 1952 (3), then the first
operation done with the support of extracorporeal pump
oxygenation by John Gibbon in 1953 (4), and cross-
circulation championed by C. Walton Lillehei in 1954 (5),
the field of surgical and interventional treatment and
palliation for CHD has exploded into the success story we
know today.
While these heroic pioneering surgical feats were
necessary to break the ice, parallel developments such
as cardiac catheterization and echocardiography in the
1950’s needed 2 decades to mature and become clinical
mainstream in the sixties to seventies, leading to further
precision in diagnosis, real-time imaging, and follow-up of
the heart. With the birth of pediatric critical care in the late
seventies, improvements in cardiopulmonary bypass (CPB)
perfusion hardware, the advent of percutaneous catheter-
based cardiac interventions and refinements in anatomical
and physiological understanding of single ventricle defects,
the stage has been set since the 1980’s for the current era
of multidisciplinary treatment of CHD. Thus, guidelines
and milestones have been established in the treatment
of virtually every single congenital cardiovascular defect
encountered in nature, ranging from near 100% survival
and freedom from reintervention or repeat surgery for the
more simple malformations, such as atrial or ventricular
septal defects, patent ductus arteriosus and coarctation, to
more complex defects with correspondingly lower peri-
operative survival and the need for continuous follow-up
and care.
Currently, in developed countries with established
programs built with the sole responsibility to care for
patients with congenital heart defects, surviving any given
intervention or surgical procedure is really expected by
caregivers and parents alike, but really comes to taking care
of what CHD really represents, which is not a cure in most
instances. Indeed, outcomes are no longer only measured by
survival to discharge from the hospital, or even by freedom
from complications which is of course an important
measure of quality of care. Now that these immediate peri-
operative goals are achieved in the vast majority of patients
who go on not only to survive, but to grow up and become
adolescents and then adults with treated CHD, the focus
has shifted towards quality of life in the mid to long-term,
developmental and learning processes, and a vast array of
medical and social issues relating to what it means to live
with “a treated heart condition”. Tremendous technological
feats at a macroscopic level which are obvious to the naked
eye have already been achieved, are still being discovered, or
being adapted and accordingly refined to help those patients
already born and treated for CHD. More importantly,
current and future focus are directed towards understanding
the genesis, genetics, and corresponding earlier diagnosis
with eventual new therapeutic strategies and targets at the
fetal stage and/or even at the molecular level, for those
Editorial
Advances and research in congenital heart disease
Ali Dodge-Khatami
Pediatric and Congenital Heart Surgery, Children’s Heart Center, University of Mississippi Medical Center, Jackson, MS, USA
Correspondence to: Ali Dodge-Khatami, MD, PhD. Chief, Pediatric and Congenital Heart Surgery, Children’s Heart Center, University of Mississippi
Medical Center, Jackson, MS, USA. Email: adodgekhatami@umc.edu.
Submitted May 19, 2016. Accepted for publication May 24, 2016.
doi: 10.21037/tp.2016.05.01
View this article at: http://dx.doi.org/10.21037/tp.2016.05.01

110 Dodge-Khatami. Advances in congenital heart surgery
patients yet unborn.
What are some of the future directions which research
could heavily influence? In many surgical repairs, from
the newborn period to adulthood, somatic growth of the
heart and vessels parallel to that of the patient must be
taken into consideration. Prosthetic materials and implants
are willingly avoided, with preference given to biological
ones. While autologous tissue from the patient itself is the
ideal material, having the advantages of being living tissue,
thereby allowing for somatic growth, resisting infection, not
requiring anticoagulation, and not inducing any rejection
phenomenon, it is not always available in the appropriate
amount or shape. The extant research and results of tissue
engineering, using various combinations of biological
scaffolds seeded with autologous stem or mature cells
are most promising, but still have a ways to go. Although
various living bio-engineered tissues have been produced
and shown to function in vitro and in vivo, either in the
myocardium, as valve substitutes, or as patch material, they
have to date failed to endure the mechanical wear and tear
of time, and therefore still need to stand the ultimate test
of acceptable longevity. Furthermore, time constraints
pertinent to harvesting cells from a given patient, treating
and culturing them in vitro and seeding onto a scaffold
which will eventually result in a functioning tissue ready for
implantation back into the patient itself, make the current
bio-engineered tissues unpractical, or definitely not a “real
time” alternative. Ideally, such autologous bio-materials
should instantly be “ready to use” in an off-the-shelf,
custom-made, tailored-to-the-patient’s-size manner, which
will hopefully be achieved through technological advances
in the near future.
In the field of neurological development, enhanced neuro-
imaging modalities have allowed better documentation of
the insults, injuries and malformations, or lack thereof, in
neonates with CHD. Indeed, it is increasingly becoming
apparent that in utero blood flow patterns specific to certain
cardiac lesions which create a relative steal of blood flow
away from the brain lead to significant cerebral lesions by
birth, and therefore already exist prior to any surgical or
interventional procedure on the heart. Although enhanced
imaging and neuro-monitoring capabilities allow for better
spatio-temporal documentation of what has already happened
and how it may evolve in time with follow-up, more needs
to be achieved in understanding exactly what processes lead
to the neurological insults, and more importantly, what
can eventually be done to influence the course of events, or
more ideally, even prevent any harm in the first place. Huge
research efforts are still needed to fully identify, understand
and hopefully influence the patho-physiology of neurological
injury and capacity for repair/regeneration in the heart-brain
axis of patients with CHD.
As the various intricate and delicate stages of embryogenesis
of the heart are better defined and understood, so also has
advanced the bold strategy to intervene and hopefully
influence certain critical key structures and blood flow
patterns in the developing heart. Intrauterine intervention,
either by percutaneous/trans-uteral catheter balloon
dilatation or by open surgical technique, has been successfully
performed, most notably on the aortic valve, in fetuses
with aortic valve stenosis, hypoplasia or atresia and variants
of hypoplastic left heart syndrome (6). The risk-benefit
ratio should take into consideration treating two patients,
the mother and the fetus, since both of the patients could
potentially suffer, and only one (the fetus) benefits. Whether
in-utero treatment techniques can reliably result in favour of
both mother and fetus remains to be demonstrated, which is
why only a few highly specialized centers are undertaking it
with promising results (6).
Although major advances have been made in the field
of genetics with regards to diagnosis which then influences
prognosis and genetic counselling, the vast majority of the
etiology of congenital heart defects remains incompletely
understood or unknown (7). Roughly 30% of CHD patients
have phenotypes which fit into syndromes including
extracardiac manifestations. That leaves about 70% of cases
in which no syndrome exists, and for whom only some have
known Mendelian inheritance (dominant or recessive).
This leaves a lot of room for the interplay of multifactorial
etiologies such as the interactions between multiple genes,
environmental factors, and spontaneous mutations, just
to name a few. Therefore, currently, there is still a time-
lag between the objectives of genetical testing in clinical
practice with a goal to assist in diagnosis, help define
prognosis and aid in parent counselling, or their value for
research purposes which may lead to insights into a disease
entity and potential future therapeutics targets. The future
interplay between clinicians and research laboratories
to bring together patterns of knowledge that fit will be
of paramount value and provide additional keys to the
understanding of the genesis/genetics of CHD.
In conclusion, the field of care for congenital heart
defects has made tremendous strides in its young infancy.
In no other field of science or medicine has so much been
accomplished in so little time, with heart defects that
were an unconditional death sentence 60 years ago, to

111Translational Pediatrics, Vol 5, No 3 July 2016
the current operative survival rates of more than 96% for
all defects considered together. We must give tribute to
bold pioneers in the early days of the 1940’s and 1950’s for
taking the biggest steps, with further refinements in the
1970’s and 1980’s to reach the point where we are today.
However, for certain defects, we are only scratching the
surface, and short-term as well as long-term outcomes
are still unsatisfactory. Owing to huge advances in
perinatal care, increasingly premature babies with complex
syndromes involving multiple organs are no longer
subject to “natural selection” and are surviving, bringing
with them an array of cardiac and associated non-cardiac
malformations that confound not only cardio-pulmonary
physiology, but require a more holistic approach to patient
care. Furthermore, although surviving an operation or
intervention for a congenital heart condition is now
expected for the vast majority of patients as neonates and
infants, the focus is shifting towards quality of life, long-
term issues, and treatment/care algorithms for adults
having survived their initial hurdles, who now represent
the majority of patients with CHD, a new fast-growing
population. Much collaboration, vision and innovation
is still needed to tackle and understand congenital heart
defects, giving providers who are privileged to be involved
in the care of these patients and families challenges for
many decades to come.
Acknowledgements
None.
Footnote
Conflicts of Interest: The author has no conflicts of interest to
declare.
References
1. Gross RE. Surgical management of the patent ductus
arteriosus: with summary of four surgically treated cases.
Ann Surg 1939;110:321-56.
2. Taussig HB, Blalock A. The tetralogy of Fallot; diagnosis
and indications for operation; the surgical treatment of the
tetralogy of Fallot. Surgery 1947;21:145.
3. Lewis FJ, Taufic M. Closure of atrial septal defects with the
aid of hypothermia; experimental accomplishments and the
report of one successful case. Surgery 1953;33:52-9.
4. Gibbon JH Jr. Application of a mechanical heart and lung
apparatus to cardiac surgery. Minn Med 1954;37:171-85;
passim.
5. Lillehei CW, Cohen M, Warden HE, et al. The direct-
vision intracardiac correction of congenital anomalies by
controlled cross circulation; results in thirty-two patients
with ventricular septal defects, tetralogy of Fallot, and
atrioventricularis communis defects. Surgery 1955;38:11-29.
6. Freud LR, McElhinney DB, Marshall AC, et al. Fetal
aortic valvuloplasty for evolving hypoplastic left heart
syndrome: postnatal outcomes of the first 100 patients.
Circulation 2014;130:638-45.
7. Chaix MA, Andelfinger G, Khairy P. Genetic testing in
congenital heart disease: A clinical approach. World J
Cardiol 2016;8:180-91.
Cite this article as: Dodge-Khatami A. Advances and research
in congenital heart disease. Transl Pediatr 2016;5(3):109-111.
doi: 10.21037/tp.2016.05.01

The achievements of congenital cardiac surgery over the
past two decades are remarkable. However success comes
at a price and occasionally the “sacrificial lamb” in this
discipline are the branch pulmonary arteries. This is not
to suggest intentional “sacrifice” however the necessity
to provide pulmonary blood flow particularly in single
ventricle palliation requires manipulation and potential
distortion of the branch pulmonary arteries (BPA’s). In a
large randomized trial assessing initial surgical palliation
for hypoplastic left heart syndrome, although antegrade
pulmonary blood flow through a Sano shunt provided an
early survival benefit over a systemic arterial-pulmonary
shunt, re-intervention rates on the BPA’s were significantly
higher in the Sano cohort (1). The impact of pulmonary
artery distortion on long-term survival in single-ventricle
patients dependent on passive pulmonary blood flow is
unclear, however, unlikely to be negligible. The optimal
approach to relieve pulmonary artery narrowing is yet to
be determined. No randomized trials comparing surgical
versus transcatheter options have been published although
non-randomized studies suggest that patients undergoing
surgical branch pulmonary arterioplasty are more likely to
require re-intervention compared to those undergoing stent
placement (2). Equally it is difficult to argue that stents
in their current format are the ideal long-term solution.
Surgical techniques and patch material may vary and hence
influence outcomes, with disappointing recent results seen
with the use of a porcine extracellular matrix patch when
used to patch the pulmonary arteries (3). The ideal material
for surgical patching, which should be pliable and easy to
handle, resistant to tearing, calcification or shrinkage, with
the potential for growth and restoration of vascular function
without the induction of scar tissue may be some way off
yet. In the meantime approaches to circumvent some of the
consequences of suture induced scaring are required.
In this issue of Translational Pediatrics, we review a
recently published novel approach to surgical reconstruction
of the BPA’s in patients with congenital heart disease (4).
Kim et al. described their use of “sutureless” patch
angioplasty for postoperative pulmonary artery narrowing
in 28 patients with a median weight of 7.3 kg, two-thirds
of whom had previous palliation for hypoplastic left heart
syndrome and 85% of whom had a concomitant superior
cavopulmonary anastomosis. The procedure involves
longitudinal opening of the stenosed BPA and enucleation
of the pre-existing patch material from the surrounding
fibrotic tissue. Multiple intimal incisions were made and
followed by stretching the vessel manually with a dilator. In
some cases the entire stenotic area was excised leaving just
the perivascular fibrotic tissue intact. The patch (bovine
pericardium) was then sutured to the perivascular fibrotic
tissue and to the aortic wall to avoid suture mediated
scaring of the intima of the pulmonary artery. Technical and
operative outcomes were excellent. The procedure avoids
extensive dissection of the pulmonary arteries which has
previously proved challenging with retro-aortic stenosis
and may also risk damage to surrounding structures.
Re-intervention was required in only one patient over
the medium-term, with follow-up imaging [computed
tomography (CT) or angiography] demonstrating some
increase in pulmonary artery dimensions at the area of
sutureless patching.
Editorial
The battleground of the stenotic branch pulmonary arteries: the
surgical approach of “less is more”
Damien P. Kenny1
, Jonathan McGuinness1
, Ziyad M. Hijazi2
1
Department of Cardiology and Cardiac Surgery, Our Lady’s Children’s Hospital, Dublin, Ireland; 2
Weill Cornell Medicine, Sidra Medical and
Research Center, Doha, Qatar
Correspondence to: Damien P. Kenny, MD. Department of Cardiology and Cardiac Surgery, Our Lady’s Children’s Hospital, Crumlin, Dublin 12,
Ireland. Email: damien.kenny@olchc.ie.
Submitted May 06, 2016. Accepted for publication May 16, 2016.
doi: 10.21037/tp.2016.05.03

The benefit of “sutureless” techniques have evolved from
pulmonary venous reconstruction surgery where exposure
of the vein to suture based trauma may lead to excessive scar
formation and restenosis (5). It is unclear if this approach
will provide similar benefits for mitigating against branch
pulmonary artery distortion in the longer-term. Some
concerns have yet to be addressed. It is unclear if the absence
of intimal tissue will promote true growth of the BPA’s, with
only patch and scar tissue remaining. The impact of suturing
to surrounding vessels, particularly the aorta may distort
the vasculature with growth or increase risk of vascular
compromise if further transcatheter intervention were to
be required. The cause of the sudden massive hemoptysis
in one patient on follow-up raises some questions about the
potential for fistula formation with less integrity to the neo-
pulmonary wall. It is also unclear if loss of vascular function
with near complete excision of the vessel, in the setting of
a circulation dependent of passive pulmonary blood flow,
may have longer-term implications. No mention is made of
the impact of the patch on follow-up surgeries, particularly
completion of the total cavopulmonary anastomosis where
distinguishing the true plane of the pulmonary artery wall
with dissection may be challenging. All things considered
however, this approach is certainly a welcome addition to the
challenge of treating complex BPA narrowing, particularly
in the context of irregular long segment stenoses where
moulding a patch to the native vessel wall, often variable
in diameter, is technically very difficult. It is also likely to
help with accessing a retro-aortic stenosis without extensive
dissection. In the end, the victor in the race to provide the
optimal solution to BPA narrowing is the one most likely to
provide the best long-term impact on normal vessel growth,
and although this technique may provide a preferable
approach in certain anatomical substrates, much work
remains to be done.
Acknowledgements
None.
Footnote
Provenance: This is a Guest Editorial commissioned
by the Section Editor Xicheng Deng (Department of
Cardiothoracic Surgery, Hunan Children’s Hospital,
Changsha, China).
Conflicts of Interest: The authors have no conflicts of interest
to declare.
Comment on: Kim H, Chan Sung S, Choi KH, et al.
Sutureless Patch Angioplasty for Postoperative Pulmonary
Artery Stenosis in Congenital Cardiac Surgeries. Ann
Thorac Surg 2016;101:1031-6.
References
1. Ohye RG, Sleeper LA, Mahony L, et al. Comparison of
shunt types in the Norwood procedure for single-ventricle
lesions. N Engl J Med 2010;362:1980-92.
2. Patel ND, Kenny D, Gonzalez I, et al. Single-center
outcome analysis comparing reintervention rates of
surgical arterioplasty with stenting for branch pulmonary
artery stenosis in a pediatric population. Pediatr Cardiol
2014;35:419-22.
3. Padalino MA, Quarti A, Angeli E, et al. Early and mid-
term clinical experience with extracellular matrix scaffold
for congenital cardiac and vascular reconstructive surgery:
a multicentric Italian study. Interact Cardiovasc Thorac
Surg 2015;21:40-9.
4. Kim H, Chan Sung S, Choi KH, et al. Sutureless Patch
Angioplasty for Postoperative Pulmonary Artery Stenosis
in Congenital Cardiac Surgeries. Ann Thorac Surg
2016;101:1031-6.
5. Yun TJ, Coles JG, Konstantinov IE, et al. Conventional
and sutureless techniques for management of the
pulmonary veins: Evolution of indications from
postrepair pulmonary vein stenosis to primary
pulmonary vein anomalies. J Thorac Cardiovasc Surg
2005;129:167-74.
Cite this article as: Kenny DP, McGuinness J, Hijazi ZM.
The battleground of the stenotic branch pulmonary arteries:
the surgical approach of “less is more”. Transl Pediatr
2016;5(3):112-113. doi: 10.21037/tp.2016.05.03

Original Article
Antegrade cerebral perfusion at 25 ℃ for arch reconstruction
in newborns and children preserves perioperative cerebral
oxygenation and serum creatinine
Bhawna Gupta1
, Ali Dodge-Khatami1
, Juan Tucker1
, Mary B. Taylor2
, Douglas Maposa3
, Miguel Urencio1
,
Jorge D. Salazar1
1
Division of Cardiothoracic Surgery, 2
Divisions of Pediatric Critical Care and Pediatric Cardiology, 3
Division of Pediatric Anesthesiology, The
Children’s Heart Center, The University of Mississippi Medical Center, Jackson, Mississippi, USA
Contributions: (I) Conception and design: All authors; (II) Administrative support: B Gupta, A Dodge-Khatami, JD Salazar; (III) Provision of
study materials or patients: B Gupta, A Dodge-Khatami, J Tucker, JD Salazar; (IV) Collection and assembly of data: None; (V) Data analysis and
interpretation: B Gupta, A Dodge-Khatami, J Tucker, JD Salazar; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All
authors.
Correspondence to: Jorge D. Salazar, MD. Division of Cardiothoracic Surgery, University of Mississippi Medical Center, 2500 North State Street,
Jackson, MS 39216, USA. Email: jsalazar@umc.edu.
Background: Antegrade cerebral perfusion (ACP) typically is used with deep hypothermia for cerebral
protection during aortic arch reconstructions. The impact of ACP on cerebral oxygenation and serum
creatinine at a more tepid 25 ℃ was studied in newborns and children.
Methods: Between 2010 and 2014, 61 newborns and children (<5 years old) underwent aortic arch
reconstruction using moderate hypothermia (25.0±0.9 ℃) with ACP and a pH-stat blood gas management
strategy. These included 44% Norwood-type operations, 30% isolated arch reconstructions, and 26%
arch reconstructions with other major procedures. Median patient age at surgery was 9 days (range,
3 days–4.7 years). Cerebral oxygenation (NIRS) was monitored continuously perioperatively for 120 hours.
Serum creatinine was monitored daily.
Results: Median cardiopulmonary bypass (CPB) and cross clamp times were 181 minutes (range,
82–652 minutes) and 72 minutes (range, 10–364 minutes), respectively. ACP was performed at a mean
flow rate of 46±6 mL/min/kg for a median of 48 minutes (range, 10–123 minutes). Cerebral and somatic
NIRS were preserved intraoperatively and remained at baseline postoperatively during the first 120 hours.
Peak postoperative serum creatinine levels averaged 0.7±0.3 mg/dL for all patients. There were 4 (6.6%)
discharge mortalities. Six patients (9.8%) required ECMO support. Median postoperative length of
hospital and intensive care unit (ICU) stay were 16 days(range, 4–104 days) and 9 days (range, 1–104 days),
respectively. Two patients (3.3%) received short-term peritoneal dialysis for fluid removal, and none required
hemodialysis. Three patients (4.9%) had an isolated seizure which resolved with medical therapy, and none
had a neurologic deficit or stroke.
Conclusions: ACP at 25 ℃ preserved perioperative cerebral oxygenation and serum creatinine for
newborns and children undergoing arch reconstruction. Early outcomes are encouraging, and additional
study is warranted to assess the impact on late outcomes.
Keywords: Antegrade cerebral perfusion (ACP); moderate hypothermia; circulatory arrest; infants; aortic arch
Submitted Apr 28, 2016. Accepted for publication May 26, 2015.
doi: 10.21037/tp.2016.06.03

Introduction
Complex aortic arch reconstruction in neonates and
children is performed typically under deep hypothermic
circulatory arrest (DHCA). This approach has enabled
successful outcomes over many decades (1), with cerebral
protection achieved by reducing brain metabolism and
oxygen requirements. The risk of injury associated with
DHCA is not clear, although long periods have been
associated with seizures and choreoathetosis (2,3). Long-
term neurological complications may manifest as impaired
neurodevelopment, with the worst outcomes being
observed in newborns with complex congenital heart lesions
in need for aortic arch reconstruction under prolonged
periods of DHCA (2,4-7). With the intent of maximizing
cerebral protection, surgical and perfusion strategies have
been developed to selectively perfuse the brain during these
operations.
Antegrade cerebral perfusion (ACP) at deep hypothermia
emerged as an adjunctive perfusion strategy to DHCA
aiming to minimize the use of circulatory arrest and offer
additional cerebral protection during arch operations.
During ACP, blood flow is supplied to the brain selectively
during the critical period of arch reconstruction, while at
least partial somatic flow is achieved through collaterals.
Somatic ischemia is theoretically lessened during arch
reconstruction and the risks of neurological and cognitive
deficits following operation are presumably reduced (8,9).
With increased experience with ACP in the field of adult
aortic arch reconstruction, a more recent evolution from
deep hypothermia toward the use of warmer temperatures
has occurred (10-12).
The use of tepid temperatures for ACP potentially
may reduce the deleterious effects associated with deep
hypothermia and rewarming (13). But this cannot be at
the expense of cerebral and somatic protection. In the
absence of a standardized nomenclature, a recent consensus
panel categorized the temperatures into ‘deep’ for a
nasopharyngeal temperature of 14.1–20 ℃, ‘moderate’ for
20.1–28 ℃ and ‘mild’ for 28.1–34 ℃ (14). Mild-moderate
hypothermia with ACP is now utilized widely in adults,
and although not supported by formal and prospective
neurocognitive outcomes data, appears to be a safe and
effective strategy for both neurological and somatic
protection for periods of less than 60 minutes (10,15,16).
In newborns and infants, extended end-to-end repair of
coarctation is performed routinely at near-normothermia
with all cerebral and systemic perfusion achieved via the
innominate artery for periods of approximately 20 minutes,
without clinically significant neurological or end-organ
injury (17). Notwithstanding, few reports evaluate the use
of moderate hypothermia for ACP in neonates and children
undergoing aortic arch reconstructions (11,12,18-20).
To this end, our specific aim was to further assess
the perioperative impact of ACP at 25 ℃ on cerebral
oxygenation and serum creatinine in newborns and children
undergoing arch reconstructions. Herein, we report our
experience and outcomes.
Methods
Institutional Review Board approval was obtained for this
retrospective study and patient/parent consent was waived.
Between 2010 and 2014, 61 patients less than 5 years of age
underwent complex aortic arch operation using moderate
hypothermia with ACP (40–60 mL/kg/min) and a pH-stat
blood gas management strategy. The medical records were
reviewed for demographics, preoperative diagnosis, and
perioperative course. The patients were categorized into
three groups: Stage I or Norwood-type operations (Stage I),
isolated aortic arch reconstructions (Arch), and aortic
arch reconstructions with other major cardiac procedures
(Arch++). Patients with obstructed pulmonary venous return
were excluded from this study.
Surgical technique
All operations were performed using a physiologic blood-
prime followed by cooling with full-flow cardiopulmonary
bypass (CPB) (150 mL/kg/min) using a 6 ℃ temperature
gradient to moderate hypothermia (25 ℃). A pH-stat
blood gas management strategy, pO2 of 150 mmHg, and
hematocrit of 30% were maintained. ACP was delivered
via the innominate artery or equivalent with flow rates of
40–60 mL/kg/min, maintaining a mean arterial pressure
appropriate for the age of the child (25–55 mmHg). During
ACP, the arch branches and descending thoracic aorta
were controlled with snares or fine clamps to maintain a
bloodless field and maintain cerebral and systemic perfusion
pressure. Upon completion of the reconstruction, de-airing,
and removal of snares or clamps, ACP was followed by re-
warming with full-flow CPB at a maximum gradient of 6 ℃.
Cerebral and somatic oxygenation monitoring
Bilateral cerebral and single somatic oximetry were

116 Gupta et al. ACP at 25 ℃
monitored continuously and recorded by near-infrared
spectroscopy (NIRS) (Somanetics, INVOS 5100C,
Covidien) in all patients, both intraoperatively and
postoperatively for 120 hours or until discharge from
the intensive care unit (ICU). The non-invasive NIRS
probe measures the regional oxygen saturation (rSO2) as a
percentage on a scale from 15% to 95%. The probes were
placed on both sides of the forehead for cerebral (left and
right) readings, and over the right flank for somatic rSO2
readings. For this study, the data were recorded at the
following time points: baseline (before CPB), start of CPB,
cooling, aortic cross-clamping, start of ACP, during ACP,
end of ACP, un-clamping, re-warming, end of CPB, and
postoperatively for 120 hourly intervals.
Clinical outcomes and serum creatinine
The intraoperative variables assessed were CPB time,
aortic cross-clamp time, ACP flow and time, and lactate
levels. Serum creatinine and lactate levels were recorded
preoperatively and postoperatively on a daily basis until
hospital discharge. Postoperative variables analyzed
included postoperative length of ICU and hospital stay,
need for extracorporeal membrane oxygenation (ECMO),
need for postoperative peritoneal dialysis or dialysis, need
for gastrostomy tube, neurological complications (seizures,
neurological deficit and stroke), and discharge mortality.
Statistical analysis
Data are shown as mean ± standard deviation (SD), median
and range (minimum, maximum), or N (%). Given the
number of patients and low incidence of complications,
additional statistical analysis was not meaningful clinically
or statistically.
Results
Patient characteristics
The characteristics for all 61 patients are outlined in Table 1.
Median age at surgery was 9 days, with 72% being neonates
and 20% infants between 1 month and 1 year of age.
Thirty-two patients were male. Among the three groups
analyzed, 27 patients (44%) underwent a Norwood-type
(Stage I) operation for hypoplastic left heart syndrome
(HLHS) or single ventricle variants with arch hypoplasia
[unbalanced atrioventricular canal, truncus arteriosus with
hypoplastic arch, transposition of the great arteries (TGA)
with hypoplastic arch, or interrupted arch]. Of these,
25/27 (93%) Stage I operations received a right ventricle-
to-pulmonary artery shunt (Sano). In the second group,
eighteen patients (30%) underwent isolated reconstruction
of the aortic arch (Arch). In the third group (Arch++),
sixteen (26%) patients underwent aortic arch reconstruction
along with other major procedures such as a Damus-
Kaye-Stansel reconstruction with bidirectional Glenn
(Comprehensive stage II), subaortic resection, ventricular
septal defect closure, aortic/truncal root replacement, or
supravalvular aortic stenosis repair.
Operative outcomes
The operative outcomes are summarized in Table 2. All
aortic arch operations were performed at a mean rectal
temperature of 25.0±0.9 ℃. Mean CPB and aortic cross-
clamp times for all sixty-one patients were 195±95 and
87±61 min, respectively. ACP was performed at a mean flow
rate of 46±6 mL/min/kg for 52±22 minutes.
Cerebral and somatic oxygenation
The cerebral and somatic NIRS (rSO2) readings are shown
Table 1 Patient characteristics
Variable All patients (N=61)
Age at surgery
Median (range) 9 days
(3 days–4.7 years)
≤1 month, N [%] 44 [72]
1–6 months, N [%] 8 [13]
6-mo–1 year, N [%] 4 [7]
1–5 years, N [%] 5 [8]
Gestational age, weeks (for ≤1 month) 38.4±1.2
Gender, male/female, N 32/29
Birth weight, kg 3.2±0.5
Prematurity <37 weeks, N 8
Birth weight <2.5 kg, N 5
Type of procedure
Stage I: Stage I or Norwood type (93%
Sano), N (%)
27 [44]
Arch: isolated aortic arch reconstruction,
N (%)
18 [30]
Arch++
: arch plus other major, N (%) 16 [26]

in Figures 1-3. Cerebral NIRS readings stayed above
baseline throughout surgery, with no clinically-significant
differences in the intraoperative NIRS readings between
the left and right cerebral hemispheres for all patients
(Figure 1). Somatic NIRS stayed above baseline during
cooling, dropped somewhat during ACP, and rebounded
quickly after ACP.
Postoperatively, cerebral and somatic NIRS remained
near or at baseline during the first 24 hours and beyond for
all groups (Figures 2,3).
Postoperative course
The postoperative outcomes for all 61 patients and by
procedure group are described in Table 3. Of the 61
patients, a total of 6 (9.8%) required ECMO. Three were
in the Stage I (Norwood) group, and the other three had
Arch++ procedures. Median postoperative lengths of
hospital and ICU stay for all sixty-one patients were 16 days
(range, 4–104 days) and 9 days (range, 1–104 days),
respectively. Two patients in the Stage I group received
temporary peritoneal dialysis postoperatively for fluid
removal. No patient required hemodialysis. None of the
patients demonstrated evidence of liver dysfunction. Three
patients (4.9%) had an isolated seizure after surgery, two
of which were confirmed by electroencephalogram. None
persisted after initiation of medical therapy. None of the
patients had a neurologic deficit or stroke. Although not the
focus of this study, representative pre- and post-operative
brain MRI imaging is demonstrated in Figure 4.
Table 2 Operative characteristics
Operative outcome All patients (N=61) Stage I (N=27) Arch (N=18) Arch++
(N=16)
Age at surgery, days 9 [3, 4.7 y] 7 [3, 47] 12.5 (4, 3.2 y) 131 (3, 4.7 y)
Weight at surgery, kg 3.5 [2.0, 16.0] 3.1 [2.0, 4.1] 3.8 [2.6, 14.0] 4.2 [2.0, 16.0]
Peak preoperative serum creatinine, mg/dL 0.5±0.1 0.5±0.2 0.4±0.1 0.4±0.1
Peak preoperative serum lactate, mmol/L 1.8±1.1 2.0±1.4 1.6±0.5 1.6±0.6
Cross clamp time, min 72 [10, 364] 86 [47, 184] 39 [10, 104] 107 [43, 364]
ACP time, min 48 [10, 123] 63 [32, 123] 36 [10, 62] 44 [22, 102]
ACP flow, mL/kg/min 46±6 44±5 48±6 48±5
Total CPB time, min 181 [82, 652] 205 [139, 328] 109 [82, 194] 192 [97, 652]
Peak intraoperative serum lactate, mmol/L 5.2±2.4 5.8±1.7 4.2±2.7 5.3±2.9
Creatinine, lactate and ACP flow are presented as mean ± SD. Age, weight, cross clamp time, ACP time and CPB time are presented as
median and range (min, max). ACP, antegrade cerebral perfusion; CPB, cardiopulmonary bypass; SD, standard deviation.
Figure 1 Intraoperative cerebral/somatic NIRS for all patients.

Figure 2 Mean cerebral and somatic NIRS during surgery broken down into subgroups. (A) Perioperative mean cerebral and somatic NIRS
for Stage I group; (B) perioperative mean cerebral and somatic NIRS for Arch group; (C) perioperative mean cerebral and somatic NIRS for
Arch++ group.
A
B
C

Figure 3 (A) Perioperative mean cerebral left NIRS by reconstruction group; (B) perioperative mean cerebral right NIRS by reconstruction
group; (C) perioperative mean somatic NIRS by reconstruction group.
A
B
C
Serum creatinine
The mean of the peak serum creatinine levels is shown
in Figure 5. The peak creatinine for all patients averaged
0.7±0.3 mg/dL. The highest postoperative creatinine of any
single patient was 1.48 mg/dL.
Discharge mortality
Overall, there were four discharge mortalities (6.6%).
One patient underwent Stage I with a 3.5-mm modified
Blalock-Taussig shunt. After an uneventful postoperative
course and chest closure, the patient was placed on ECMO

Figure 4 Pre- and Postoperative MRI brain imaging.
Table 3 Postoperative outcomes
Postoperative outcome All patients (N=61) Stage I (N=27) Arch (N=18) Arch++ (N=16)
Discharge mortality, N (%) 4 (6.6%) 2 (7.4%) 0 2 (12.5%)
Need for ECMO, N (%) 6 (9.8%) 3 (11.1%) 0 3 (18.8%)
ICU stay, days 9 [1, 104] 12 [6, 104] 5 [1, 43] 8 [2, 63]
Postop hospital stay, days 16 [4, 104] 22 [11, 104] 11 [4, 45] 10 [4, 78]
Peak postop serum creatinine until discharge, mg/dL 0.7±0.3 0.8±0.3 0.6±0.2 0.6±0.2
Peak 24 hr postoperative serum lactate, mmol/L 3.9±2.3 5.0±2.7 2.8±1.3 3.4±1.6
Use of temporary peritoneal dialysis, N (%) 2 (3.3%) 2 (7.4%) 0 (0%) 0 (0%)
Need for G-tube, N (%) 15 (24.6%) 11 (40.0%) 3 (20.0%) 1 (6.2%)
Postoperative seizures, N (%) 3 (4.9%) 1 (3.7%) 1 (5.5%) 1 (6.2%)
Neurologic deficit/stroke, N (%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Serum creatinine and lactate are presented as mean ± SD. ICU and postoperative hospital stay are presented as median and range (min,
max). ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; Postop, postoperative; G-tube, gastrostomy tube; SD,
standard deviation.
Pre-op MRI (Baby M)
Post-op MRI (Baby M)
on postoperative day (POD) 6 for respiratory distress
and ultimately expired on POD 55. The second patient
underwent late stage I with Sano after presenting at 6 weeks
of age. Despite a favorable neurological and hemodynamic
result, the child died of chronic respiratory failure on POD
104. The third patient underwent Stage I and interrupted
aortic arch repair. Initially the child did well neurologically
and hemodynamically but was placed on ECMO on POD 4
for sudden cardiac arrest. During ECMO wean, the circuit
clotted acutely and the child died on POD 8. The fourth
patient underwent redo truncal valve replacement and arch
reconstruction. The patient was placed on post-operative
ECMO for bleeding and inability to separate from CPB
from pulmonary dysfunction. The child separated from

ECMO but ultimately expired on POD 35.
Discussion
Deep hypothermic circulatory arrest is the traditional
approach for operations involving aortic arch reconstruction
in adults and children, acknowledging the potential for
neurological complications including cognitive deficits. The
transition from the DHCA paradigm toward ACP with deep
hypothermia was aimed to maximize cerebral protection
during arch operations while minimizing any morbidity.
Antegrade cerebral perfusion is used now by many centers
as a perfusion adjunct under deep hypothermia to minimize
the use of circulatory arrest during neonatal aortic arch
reconstruction (21), with the expectation of mitigating
neurological and somatic morbidity. A comparison of
DHCA alone versus continuous low-flow cerebral perfusion
in infants has suggested more neurological perturbations
and a greater likelihood of clinical seizures in the early
postoperative period of the DHCA alone group (3). Other
reports advocate the use of ACP over DHCA alone to not
only attenuate neurological morbidity but also to achieve
somatic protection during arch reconstruction (5,22-25).
However, other reports question the advantage of ACP
over DHCA alone, detecting no difference in the incidence
of new white matter injury or cerebral ischemic lesions
postoperatively, nor any benefit on psychomotor and mental
development status between the two groups of ACP versus
DHCA alone (26-30).
It is worth mentioning that even though ACP is used
routinely in many centers, there exist wide variations in the
specific details of the perfusion strategy. ACP flow rates,
blood gas temperature correction (pH versus alpha stat), time
required for the repair, hematocrit, pO2, and even cannulation
strategies vary significantly, making it challenging to evaluate
the benefit of cerebral perfusion during arch repairs. Despite
the lack of a standardized protocol for ACP and some
inconsistency in the reported results, there does appear to be
an increasing trend toward ACP (with deep hypothermia)
over DHCA for neonatal arch reconstruction (31).
The optimal temperature for complex aortic arch
reconstructions with ACP remains a topic of debate. Many
adult centers have shifted toward the use of mild-to-moderate
temperatures with encouraging results (10,15,32-35).
While conclusive evidence is lacking, these encouraging
outcomes coupled with shorter CPB times and avoiding the
morbidity of deep hypothermia have led to the increasing
clinical acceptance of tepid ACP for arch repair in adults.
Moderate hypothermia with ACP has been explored in
Europe and Asia for neonatal arch operations, although
the typical practice in North America has been to use deep
hypothermia with ACP or DHCA alone. Oppido et al.
reported 17% early mortality and 8.5% late deaths over a
follow-up of up to 50 months in a group of 70 consecutive
neonates who underwent the Norwood procedure or aortic
arch repair at a nasopharyngeal temperature of 25 ℃ with
ACP (18). Only one patient had postoperative seizures.
The authors suggested ACP to be an effective and reliable
perfusion strategy that provides a longer safe period for arch
repairs and minimizes neurological complications without
Figure 5 Peak perioperative creatinine for all patients.

the need for deep hypothermia. Likewise, Lim et al. (11),
Dodge-Khatami et al. (12), Miyaji et al. (20) and Ly et al. (36)
demonstrated in neonates and infants the effectiveness of
antegrade cerebral perfusion at moderate hypothermia at
preserving both cerebral and somatic tissue oxygenation.
Previously, we evaluated moderate (25 ℃) and deep
(18 ℃) hypothermia with ACP in a piglet model for arch
operation (37-39). These studies demonstrated improved
neuroprotection at 18 and 25 ℃ with ACP as compared
to DHCA alone, with shorter CPB times at 25 ℃, and
laid the foundation for our clinical practice of moderate
hypothermia with ACP during neonatal aortic arch repair.
We have employed moderate hypothermia (25 ℃) with
ACP for all aortic arch reconstructions at the University
of Mississippi Medical Center since program inception in
April of 2010.
The ideal flow rate for ACP is dependent on many factors
and remains to be established. Although the cited literature
varies widely in range for ACP from 10 to 100 mL/kg/min,
studies utilizing NIRS technology or visual light spectroscopy
have indicated that ACP flow rates of greater than
30 mL/kg/min are sufficient to maintain adequate cerebral
and somatic oxygen saturations (12,19,40). Admittedly, these
findings must be evaluated within the context of temperature
and blood gas management (pH versus alpha stat) among
other factors. We use ACP at a flow rate of 40–60 mL/kg/min
under NIRS guidance to monitor both cerebral and
somatic oxygen levels. In the current study, NIRS supports
the effectiveness of ACP at 25 ℃ systemic cooling in
maintaining adequate cerebral and lower body perfusion.
Although somatic NIRS dropped during ACP, they remained
close to baseline levels, suggesting that an ACP flow at
40–60 mL/kg/min was sufficient in maintaining adequate
perfusion through collaterals to the lower body and
attenuating somatic ischemia during arch operation at 25 ℃.
This is further supported by favorable postoperative lactate
and serum creatinine levels.
Conclusions
The present study suggests that moderate hypothermia
(25 ℃) with ACP preserves perioperative cerebral
oxygenation and serum creatinine in neonates, infants, and
children for complex aortic arch operations.
Limitations
The study is limited by the lack of a control group with
DHCA alone or ACP at deep hypothermia. Intra-operative
electroencephalogram, which does not always correlate with
right and left cerebral NIRS, was not performed, and could
have disclosed abnormal neurological activity undetected by
NIRS. Long-term neurodevelopmental follow-up of these
children is required to evaluate the late outcomes of ACP
with warmer temperatures and make formal comparison
with strategies at 18 ℃.
Acknowledgements
None.
Footnote
to declare.
Ethical Statement: Institutional Review Board (2014-0107)
approval was obtained for this retrospective study and
patient/parent consent was waived.
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Cite this article as: Gupta B, Dodge-Khatami A, Tucker J,
Taylor MB, Maposa D, Urencio M, Salazar JD. Antegrade
cerebral perfusion at 25 ℃ for arch reconstruction in newborns
and children preserves perioperative cerebral oxygenation
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Original Article
How to set-up a program of minimally-invasive surgery for
congenital heart defects
Juan-Miguel Gil-Jaurena1,2
, Ramón Pérez-Caballero1,2
, Ana Pita-Fernández1,2
, María-Teresa González-
López1,2
, Jairo Sánchez3
, Juan-Carlos De Agustín4
1
Department of Pediatric Cardiac Surgery, Hospital Gregorio Marañón, Madrid, Spain; 2
Department of Instituto de Investigación Sanitaria Gregorio
Marañón, Madrid, Spain; 3
Department of Pediatric Cardiac Surgery, Instituto Cardiológico, Bucaramanga, Colombia; 4
Department of Pediatric
Surgery, Hospital Gregorio Marañón, Madrid, Spain
Contributions: (I) Conception and design: JM Gil-Jaurena; (II) Administrative support: R Pérez-Caballero, JC De Agustín; (III) Provision of study
materials or patients: A Pita-Fernández , MT González-López; (IV) Collection and assembly of data: JM Gil-Jauren, MT González-López; (V) Data
analysis and interpretation: JM Gil-Jaurena, JC De Agustín; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Correspondence to: Juan-Miguel Gil-Jaurena. Pediatric Cardiac Surgery, Hospital Gregorio Marañón, C/O´Donnell nº50, 28009, Madrid, Spain.
Email: giljaurena@gmail.com.
Background: Mid-line sternotomy is the commonest incision for cardiac surgery. Alternative approaches
are becoming fashionable in many centres, amidst some reluctance because of learning curves and overall
complexity. Our recent experience in starting a new program on minimally invasive pediatric cardiac surgery
is presented. The rationale for a stepwise onset and the short-medium term results for a three-year span are
displayed.
Methods: A three-step schedule is planned: First, an experienced surgeon (A) starts performing simple
cases. Second, new surgeons (B, C, D, E) are introduced to the minimally invasive techniques according
to their own proficiency and skills. Third, the new adopters are enhanced to suggest and develop further
minimally invasive approaches. Two quality markers are defined: conversion rate and complications.
Results: In part one, surgeon A performs sub-mammary, axillary and lower mini-sternotomy approaches
for simple cardiac defects. In part two, surgeons B, C, D and E are customly introduced to such incisions. In
part three, new approaches such as upper mini-sternotomy, postero-lateral thoracotomy and video-assisted
mini-thoracotomy are introduced after being suggested and developed by surgeons B, C and E, as well as an
algorithm to match cardiac conditions and age/weight to a given alternative approach. The conversion rate
is one out of 148 patients. Two major complications were recorded, none of them related to our alternative
approach. Four minor complications linked to the new incision were registered. The minimally invasive to
mid-line sternotomy ratio rose from 20% in the first year to 40% in the third year.
Conclusions: Minimally invasive pediatric cardiac surgery is becoming a common procedure worldwide.
Our schedule to set up a program proves beneficial. The three-step approach has been successful in our
experience, allowing a tailored training for every new surgeon and enhancing the enthusiasm in developing
further strategies on their own. Recording conversion-rates and complications stands for quality standards. A
twofold increase in minimally invasive procedures was observed in two years. The short-medium term results
after three years are excellent.
Keywords: Sternotomy; minimally invasive; sub-mammary; axillary; thoracoscopy; video-assisted
Submitted Apr 19, 2016. Accepted for publication May 25, 2016.
doi: 10.21037/tp.2016.06.01
View this article at: http://dx.doi.tp/10.21037/tp.2016.06.01

126 Gil-Jaurena et al. Setting-up a congenital minimally-invasive program
Introduction
Surgical closure of cardiac defects via a full mid-line
sternotomy has been considered the gold standard for over
50 years. The rise of interventional cardiology and new
techniques like laparoscopy or thoracoscopy have prompted
some groups to explore alternative approaches to median
sternotomy (1-7). New adopters and reluctant ones have
their own reasons. Added complexity, longer overall and
ischemic times and even results account for the balance of
the latter.
Among the most frequent alternative approaches (Figure 1)
we find: lower mini-sternotomy (8-11), right sub-mammary
(1,12-16), postero-lateral thoracotomy (17,18) and right
axillary incisions (19-23). Main advantages are cosmesis and
earlier recovery, as well as saving blood products and lower
infection rates. On the other hand, a steep learning curve
and technical difficulties in handling some steps (myocardial
protection, de-airing maneuvers, and so on) discourage
many surgeons to include these minimally invasive
procedures within their routine practice.
Trying to schedule a program for starting and teaching
minimally invasive pediatric cardiac surgery is a step
forward. Few reports can be found in the literature on
the topic, if any, except for the right mini-thoracotomy
approach employed for mitral repair (23-27) in adult
cardiac surgery. In the next paragraphs, we will depict our
experience in developing a minimally invasive pediatric
cardiac surgery program, pointing out the steps followed as
well as the insights provided by the new adopters.
Methods
Upon arrival to a medium-volume centre in which
approximately two hundred pump cases per year are
carried out, Surgeon A is expected to develop a program
of minimally-invasive pediatric cardiac surgery. He has
been performing minimally invasive procedures for twelve
years in two previous institutions and has produced several
papers on the topic (6,16,22,23,28,29) , as well as many
presentations in local meetings.
The strategy to establish a new program is split in three
parts, assuming some overlapping rather than a formal
schedule in a three year analysis:
(I) Performing minimally invasive cases (surgeon A)
with every member of the surgical team (surgeons,
anesthesiologists, perfusionists, scrub nurses) to let
them become familiar and confident with the new
approaches;
(II) Introducing new surgeons to minimally invasive
surgery in a stepwise and customized way,
according to expertise and skills;
(III) Developing new strategies together, particularly
enhanced by the young staff members.
On the other hand, some quality indicators will be
measured, such as:
(I) Conversion rate. If so, was it to sternotomy or
another incision?
(II) Complications. Trying to figure out whether the
alternative approach is to blame for the drawback
or if any other cause was responsible for it.
To begin with, a minimally invasive incision will be
A B
C D
Figure 1 Range of approaches introduced by the leading surgeon.
(A) Full mid-line sternotomy; (B) lower mid-line sternotomy;
(C) right sub-mammary approach; (D) right axillary incision.

defined as “surgical approach other than full mid-line sternotomy
to perform open heart surgery with extracorporeal circulation”.
Three main surgical approaches were introduced by
surgeon A: sub-mammary, axillary and lower mini-
sternotomy. A single alternative incision gives way either to
cannulation maneuvers and correction, with the philosophy
of “same steps, same tools, same risks, different approach”. Later
in the program (as will be thoroughly displayed in Results
and Discussion) several new approaches were added: upper
mini-sternotomy, postero-lateral thoracotomy and video-
assisted mini-thoracotomy (for which several ports were
necessary). Not included in the tables, some off-pump cases
via thoracotomy and thoracoscopy were performed, as some
experience was acquired by the team.
Before starting any procedure, the proposed incision is
drawn with a sterile pen for teaching purposes. Should an
enlargement or conversion be needed, security margins
are settled (e.g., lower mini-sternotomy enlargement to
full sternotomy, or axillary incision conversion to postero-
lateral one). Brief description of the minimally invasive
approaches:
(I) Sub-mammary. Supine position with the right
shoulder slightly elevated and the right arm
suspended over the head. Skin incision under the
right sub-mammary crease (or 6th intercostal space
in children). En-block dissection of subcutaneous
tissue and pectoral muscle (30,31). Cage-rib entry
in the 4th intercostal space. Full cannulation and
correction under cardioplegic arrest (Figures 1C,2);
(II) Axillary. Decubitus lateral position with the right
arm suspended over the head. Skin incision in the
axillary groove, between anterior and posterior lines.
Serratus and latissimus dorsi muscles sparing (28)
technique. Cage-rib entry in the 4th intercostal
space. Full cannulation and correction under
cardioplegic arrest (Figures 1D,3);
(III) Lower mini-sternotomy. Supine position. Skin
vertical incision below an imaginary line connecting
both nipples. Partial lower sternotomy. Regular
spreader plus cephalad traction of the sternum.
Full cannulation and correction under cardioplegic
arrest (Figures 1B,4);
(IV) Upper mini-sternotomy. Supine position. Skin vertical
incision above an imaginary line connecting both
nipples. Partial upper sternotomy. Full cannulation
and correction under cardioplegic arrest;
(V) Postero-lateral thoracotomy. Decubitus lateral
position with the right arm suspended over the
head. Skin incision between anterior axillary line
and spine (the tip of the scapula being the mid-
point). Cage-rib entry in the 4th intercostal space.
Full cannulation and correction under cardioplegic
arrest (Figure 3A);
(VI) Video-assisted mini-thoracotomy. Supine position
with the right shoulder slightly elevated and the
right arm secured below the axilla. Mini-skin
incision under the right sub-mammary crease.
Right jugular and right femoral (arterial and
venous) cannulation to institute by-pass. Additional
ports for video-assistance, aortic clamp and others.
A B
A B
Figure 2 Sub-mammary approach in an adolescent female. Note
the landmarks (A) and final aesthetic result (B).
Figure 3 Right horizontal axillary incision. Note the landmarks
between the nipple and the tip of the scapulla as well as the
proposed conversion to a postero-lateral incision if needed (A).
Final result six months later (B).

Correction under cardioplegic arrest.
Results
Part one
Surgeon A began his program with sub-mammary, axillary
and lower mini-sternotomy cases alternatively, according
to age/weight and cardiac condition of every patient. This
way, ventricular septal defect (VSD) cases were corrected by
mini-sternotomy, atrial septal defect (ASD) patients through
an axillary approach, and women with well-defined sub-
mammary groove were entered by a sub-mammary incision.
The initial three months was time enough to get everyone
in the cardiac team comfortable with the changes.
Part two
Surgeons B, C and D were sequentially introduced to
lower mini-sternotomy and sub-mammary approaches,
according to their own interest and skills. Simple cases
(ostium secundum ASD) were selected for this purpose to
begin with, followed by VSD closure through lower mini-
sternotomy in a customized pattern for every surgeon. By
the end of the first year, all surgeons had already performed
ASD and VSD cases through lower mini-sternotomy and
some ASD closures through a sub-mammary approach.
Surgeon D moved to a different Center in another
Country and was substituted by surgeon E, who took up
quickly the same method of learning, following the way of
surgeons B and C.
On the other hand, Surgeons B and C considered the
axillary approach rather cumbersome, and suggested
starting a postero-lateral one before attempting the former.
Part three
Surgeon C introduced the upper mini-sternotomy approach
for aortic valve surgery with the advice of an adult cardiac
surgeon.
As previously stated, the right postero-lateral thoracotomy
was suggested by surgeons B and C (and surgeon E, later on)
as an initial step before taking up the axillary incision.
Surgeon B suggested moving forward and attempting a
thoracoscopic approach. He reviewed the literature (32-37)
and contacted a pediatric surgeon with experience in
the field from our own Center. After assisting him in
thoracoscopic patients (pediatric surgery) and attending a
specific course in minimally-invasive thoracoscopy (surgeons
B and C), a new program was started.
Surgeon E displayed a sort of algorithm for case-approach,
according to age/weight & cardiac defect, resulting in a
tailored minimally invasive approach for any given patient.
Table 1 depicts the amount of patients operated on by
a minimally invasive approach by every surgeon during
the three consecutive years. When compared to the total
amount of patients, the ratio of mini-invasive to total pump-
cases increased twofold between 2013 and 2015. We have
to take into account that 2014 was the first year for Surgeon
E, which could explain why the figures are so close between
2013 (20%) and 2014 (22.5%), rather than displaying a
steady progression along the three year span.
Increase in percentage of mini-invasive pump cases.
(I) 2013: 40/201 (20%)
(II) 2014: 40/178 (22.5%)
(III) 2015: 68/166 (40%)
Table 2 displays the different approaches by every
Table 1 Number of procedures performed by surgeon and year
Surgeon
Year
Total
2013 2014 2015
A 15 12 21 48
B 7 8 6 21
C 10 12 22 44
D 8 8
E 8 19 27
Total 40 40 68 148
Figure 4 Lower mid-line sternotomy. Full mid-line sternotomy
(upper left) as compared to lower mini-sternotomy (lower left).
Result at discharge on 7th
postoperative day.
A
B
C

surgeon. All of us are confident with the lower mini-
sternotomy and sub-mammary ones. Only surgeon A is
performing the axillary incision up to now, because the
remaining staff members feel more comfortable with the
postero-lateral approach. The upper mini-sternotomy,
introduced by surgeon C, has been taken up by surgeons
B and E as well, for aortic valve patients. The video-
assisted thoracotomy, led by surgeon B, is applied for ostium
secundum ASD patients by surgeons B and C.
Table 3 shows the distribution of diagnosis and surgeons.
Simple conditions, like ASD (ostium secundum, sinus venosus,
ostium primum) and VSD have been performed by every
surgeon (excepting surgeon D, who left earlier). To sum
up, these simple cases account for more than 80% of the
whole number of minimally-invasive pump cases. Regarding
VSD’s alone, which has been approached by lower mini-
sternotomy, the progression has been steady along the three
years with a well-defined step up:
(I) 2013: 32/40 (80%)—12 VSD
(II) 2014: 35/40 (87%)—12 VSD
(III) 2015: 58/68 (82%)—20 VSD
More complex cases (complete atrio-ventricular septal
defect, subaortic myectomy (Morrow), scimitar syndrome,
tricuspid valve repair) have been performed by surgeon A,
expanding the indications of minimally invasive surgery as
experience is gained.
Table 4 summarizes the data relating to the approach
and cardiac defect, independently of the surgeon. ASD and
VSD are the commonest conditions, as expected. Lower
mini-sternotomy is the most prevalent approach, given its
simplicity (in fact, it is the first alternative incision learned)
and the wide range of cardiac defects corrected through this
pathway. The sub-mammary incision has been used for any
type of ASD and few others; the axillary approach for ostium
secundum and sinus venosus ASD, only. At the moment, the
upper mini-sternotomy is indicated for aortic valve purposes
and the video-assisted thoracotomy for ostium secundum
defects.
Not included in Table 4 which describes pump cases
only, some patients were operated on via left thoracotomy
without cardio-pulmonary by-pass (one sling left pulmonary
artery, two patients with anomalous drainage of left upper
pulmonary veins) and video-assisted thoracoscopy [one
pericardial window and one left atrial appendage ablation (38)
plus clip-exclusion].
Conversion rate
An axillary approach for a sinus venosus ASD had to be
converted to a postero-lateral one (just enlarging the skin
incision backwards and splitting the latissimus dorsi muscle).
Despite the conversion, the postero-lateral approach can
still be considered a minimally invasive one. No other
conversion was required.
Complications
An ostium primum patient died because progression of
diffuse pulmonary vein stenosis three months after repair. A
VSD patch-closure developed aortic regurgitation (excessive
trimming of redundant tricuspid tissue which happened to
be stuck to an aortic cusp) and was re-operated two days
later. A valve repair proved unsuccessful and ended up in
a Ross-Konno procedure. Two patients (ASD and VSD)
required revision for bleeding. The initial approach in all
four cases had been via lower mini-sternotomy.
One ASD patient approached via sub-mammary incision
developed transient phrenic palsy and continuous pleural
effusions. An analysis of the pleural fluid showed lidocaine
and, after removal of the trans-thoracic anesthetic line
Table 2 Number of procedures performed by surgeon and approach
Surgeon
Approach
Total
Lower mini-sternotomy Sub-mammary Axillary
Lateral-posterior
thoracotomy
Upper mini-sternotomy Thoracoscopy
A 17 6 22 3 48
B 10 4 3 1 3 21
C 25 11 2 4 2 44
D 7 1 8
E 19 4 2 2 27
Total 78 26 22 10 7 5 148

(which was dislodged), both effusion and phrenic palsy
resolved. A 55-kg child developed compartment syndrome
in the right leg after peripheral cannulation for a video-
assisted thoracotomy ASD repair. It was the only case in
whom the femoral artery was directly cannulated instead of
a graft interposition.
Discussion
Many groups have shifted towards the minimally invasive
surgical approaches in pediatrics (1-7). The rationale,
beyond cosmesis, is offering the same results with new
incisions, when catheter-based interventional procedures
are also difficult or contra-indicated. Maybe the future
will rely on totally robotic (32) or endoscopic (33-37)
surgery, but, for the time being, offering alternative
approaches is interesting. Some teams are keen on a single
particular approach, whereas others prefer to be familiar
with many of them (4-6). Whether this is a strategy or
a matter of evolution is beyond the scope of this paper.
Currently, the range of incisions different from a full
mid-line sternotomy is rich enough to provide us many
options. Interestingly, among the literature reviewed,
some papers underline the steps to set up programs
(24-27). Particularly relevant is the publication by
Bonaros et al. (32), in which the authors split every
procedure in several parts and analyze them separately, so
as to accurately depict anyone´s learning curve. Not only
did we need to start a new program, but also to teach and
enhance our young staff to develop their own ideas.
The three-step approach to introduce a program of
minimally invasive surgery in a new place has proved
successful for several reasons. First of all, the results are
good and patients/parents are satisfied. Part one (surgeon A
introducing the program) allows all members in theatre to
get in touch with the novelty, and surgeon A to realize who is
enthusiastic and who is reluctant. This way, approaches could
be decided according to individual skills and preferences in
customized patterns in part two (surgeons B, C, D and E
being introduced). Most important was the honest attitude of
Table 3 Number of procedures performed by surgeon and diagnosis
Surgeon
Procedure
Total
OS ASD SV ASD OP ASD VSD CAVSD Aortic Others
A 18 5 4 11 7 3 48
B 8 2 3 7 1 21
C 18 3 5 14 4 44
D 6 1 1 8
E 8 4 5 8 2 27
Total 58 14 18 41 7 7 148
ASD, atrial septal defect; OS, ostium secundum; SV, sinus venosus; OP, ostium primum; VSD, ventricular septal defect; CAVSD, complete
atrio-ventricular septal defect.
Table 4 Relationship between approach and diagnosis along the study period
Approach
Procedure
Total
OS ASD SV ASD OP ASD VSD Others
Lower mini-sternotomy 17 1 15 41 4 78
Sub-mammary 16 4 3 3 26
Axillary 17 5 22
Upper mini-sternotomy 7 7
Lat-post thoracotomy 3 4 3 10
Thoracoscopy 5 5
Total 58 14 18 41 17 148
ASD, atrial septal defect. OS, ostium secundum; SV, sinus venosus; OP, ostium primum; VSD, ventricular septal defect.

the staff, not assuming to tackle incisions considered difficult
(e.g., axillary one) and suggesting new approaches (part three).
As responsible of the team, surgeon A considered not to get
involved in the new programs of upper mini-sternotomy for
aortic valve cases and video-assisted thoracotomy for ASD
patients. The rationale was to let surgeons B and D lead
their own projects before incorporating new forthcoming
members (E and A): pupils became teachers.
More complex cases were added as experience was gained.
Thus, particularly in the last of the three years, the young
surgeons were taking up simple cases while surgeon A was
performing difficult ones (AVSD, scimitar). As a result, the
percentage of minimally invasive cases rose to 40%, doubling
the initial rate of 20% during the first year. The lesson is to
couple any single patient to a surgeon who is keen either on
the defect or on a particular approach, so as to match them in
the algorithm of mini-invasive surgery (6,38,39).
Regarding the conversion rate, only one patient had
to be switched. The take-home message in a minimally
invasive program is trying to convert any patient (when
needed) to another minimally invasive approach in an
expeditious way. The incision was converted from axillary
to postero-lateral incision (again, minimally invasive) by just
prolonging posteriorly the already drawn surgical mark and
severing the latissimus dorsi muscle. The new program of
video-assisted mini-thoracotomy is growing-up under the
readiness to convert incisions to a full sub-mammary one, if
needed. To date, it has not been necessary to covert a mini-
thoracotomy to full mid-line sternotomy.
Before embarking on a minimally invasive program, one
has to assume that any drawback is going to be regarded as
linked to the alternative approach. Whether it is true or not
is irrelevant, unless invasive and minimally-invasive patients
are matched. Some of the minor complications we found
were definitely related to the approach, like the transient
phrenic palsy and the compartment syndrome (40). We
have learned how to avoid them (41) in the future.
After gathering some experience, the question is how to
move forward with the program? There is no clear answer,
since not all surgeons are at the same level of proficiency,
or are still in their learning curve. Thinking in terms of
contraindications rather than indications, as a last step of
training, could be a reasonable marker. In other words,
we are not expecting for the “perfect patient” to come and
be an ideal candidate for a minimally invasive approach.
We rather think about the contraindications, if any, for a
minimally invasive procedure in every patient.
The enthusiasm showed by the team members towards
new alternative approaches was overwhelming. Not only
did the young surgeons take up the new methods quickly
(part two), but they quickly suggested new ones to be
introduced (part three). To be honest, I had to change
my mind from the aphorism “same steps, same tools, same
risks, different approach” after the video-assisted mini-
thoracotomy program was started. The shift from a
different single incision to multi-small approaches one
was not in my mind previously, but deserves all credit
because it stands for a new paradigm of surgery. The more
alternative approaches (5,39) we can offer, the better for
the cosmesis of the patients.
Conclusions
Minimally invasive pediatric cardiac surgery is currently
becoming a routine practice in many centers worldwide.
The different approaches need their own learning
curve, either straightforward or a steep one. Our recent
experience demonstrates that a comprehensive, three-step
schedule allows a safe and custom-made approach to train
new surgeons in the field. and enhances enthusiasm in
developing further strategies on their own.
A record of conversion-rate and complications should be
used as marker of performance and quality standard. The
new adopters can take their own training pace according
to their level and skills. Interestingly, the wider the offer
of approaches, the more ideas come up for new alternative
minimally invasive methods. A twofold increase in minimally
invasive procedures was observed in two years. The short-
medium term results after three years are excellent.
Acknowledgements
The authors would thank the theatre staff for their patience
and suggestions.
Footnote
to declare.
Ethical Statement: The study was approved by our
institutional ethics committee.
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Cite this article as: Gil-Jaurena JM, Pérez-Caballero R, Pita-
Fernández A, González-López MT , Sánchez J, De Agustín JC.
How to set-up a program of minimally-invasive surgery for
congenital heart defects. Transl Pediatr 2016;5(3):125-133. doi:
10.21037/tp.2016.06.01

Introduction
Mortality and morbidity of congenital cardiac procedures
have always been an issue for cardiac surgeons since
the very first operation on cardiopulmonary bypass.
Technical improvement in extracorporeal circulation,
increased knowledge in physiology and pathophysiology
of cardiopulmonary bypass and special organ protection
strategies have helped to reduce the incidence of
complications and death to an acceptable rate. However,
they are still present and need to be tackled every day. Since
Bellinger, Newburger and Jonas published their landmark
studies about neurological outcomes after arterial switch
operations (1-4), perfusion strategies, especially for aortic
arch corrections, have been more and more modified to
avoid the potential deleterious effects of deep hypothermic
circulatory arrest (DHCA) (5-9). Several alternative
perfusion regimens of body and brain have been suggested
and were implemented into clinical practice more or less
successfully, so that we have learned a lot about possible
benefits and potential new complications when mal- or
hypo-perfusion of organs occur. To our opinion, monitoring
and visualization of end organ oxygen supply and blood-
flow is of utmost importance and not only of scientific
interest.
Cerebral protection during aortic arch repair is currently
performed by either deep hypothermic circulatory arrest or
regional cerebral perfusion (RCP) via the innominate artery.
Both completely distinct cardiopulmonary bypass techniques
were unable to demonstrate a significant difference in
randomized controlled trials regarding the incidence
of perioperative cerebral injury or neurodevelopmental
Review Article
Goal-directed-perfusion in neonatal aortic arch surgery
Robert Anton Cesnjevar1
, Ariawan Purbojo1
, Frank Muench1
, Joerg Juengert2
, André Rueffer1
1
Department of Pediatric Cardiac Surgery, 2
Department of Pediatrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-
Nuernberg, Erlangen, Germany
Contributions: (I) Conception and design: All authors; (II) Administrative support: RA Cesnjevar, A Rueffer; (III) Provision of study materials
or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: RA Cesnjevar, A Rueffer; (VI)
Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Correspondence to: Robert Cesnjevar, MD, PhD. Department of Pediatric Cardiac Surgery, University Hospital Erlangen, Friedrich Alexander
University Erlangen-Nuernberg, Loschgestraße 15, 91054 Erlangen, Germany. Email: robert.cesnjevar@uk-erlangen.de.
Abstract: Reduction of mortality and morbidity in congenital cardiac surgery has always been and remains
a major target for the complete team involved. As operative techniques are more and more standardized and
refined, surgical risk and associated complication rates have constantly been reduced to an acceptable level
but are both still present. Aortic arch surgery in neonates seems to be of particular interest, because perfusion
techniques differ widely among institutions and an ideal form of a so called “total body perfusion (TBP)”
is somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory arrest (DHCA), regional
cerebral perfusion (RCP/with cardioplegic cardiac arrest or on the perfused beating heart) and TBP exist
in parallel and all carry an individual risk for organ damage related to perfusion management, chosen core
temperature and time on bypass. Patient safety relies more and more on adequate end organ perfusion on
cardiopulmonary bypass, especially sensitive organs like the brain, heart, kidney, liver and the gut, whereby
on adequate tissue protection, temperature management and oxygen delivery should be visualized and
monitored.
Keywords: Congenital heart disease; regional cerebral perfusion (RCP); organ protection; neonatal arch surgery
Submitted Jun 12, 2016. Accepted for publication Jul 06, 2016.
doi: 10.21037/tp.2016.07.03

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