SURGERY

REVIEW

Comparison of Hybrid and Norwood Strategies in

Hypoplastic Left Heart Syndrome
Hideyuki Kato, MD, Osami Honjo, MD, PhD, Glen Van Arsdell, MD, Christopher A. Caldarone, MD
Division of Cardiovascular Surgery, Hospital for Sick Children, Labatt Family Heart Center
Received 12/12/2011, Reviewed 27/12/2011, Accepted 1/1/2012
Key words: Hybrid strategy, Norwood strategy, single ventricle, hypoplastic left heart syndrome
DOI: 10.5083/ejcm.20424884.70

ABSTRACT

CORRESPONDENCE

Current surgical palliation for neonates with single ventricle physiology includes Norwood-based
and Hybrid-based surgical strategies. When transplantation is not available, clinicians must choose
between these two strategies with distinctly different learning curves and risk profiles. The Norwood
strategy has evolved over several decades while the rising popularity of the Hybrid strategy is a
much more recent addition to our therapeutic options. Based upon the premise that avoiding cardio
pulmonary bypass in the neonatal period and deferral of aortic arch reconstruction until a second
stage procedure have an important influence on outcomes, the Hybrid strategy has compelling
theoretical advantages and disadvantages in comparison to the Norwood strategy. The purpose
of this review is to summarise the currently available data to support or refute the theoretical
advantages of the Hybrid strategy within the context of the Norwood strategy.

Christopher A. Caldarone, MD,

Professor and Chair,
Division of Cardiac Surgery,
University of Toronto,
Watson Family Chair in
Cardiovascular Science
Labatt Family Heart Center,
Hospital for Sick Children,
555 University Avenue,
Toronto, Ontario, Canada,
M5G 1X8

INTRODUCTION
The Norwood-based strategy for single ventricle
palliation has improved with technical innovations and refinements over the last decades;
such as regional cerebral perfusion during aortic
arch reconstruction [1], placement of a right ventricle-to-pulmonary artery (RV-PA) shunt rather
than a systemic-to-pulmonary shunt [2, 3], and
the concept of aggressive afterload reduction to
maximise oxygen delivery following Norwood
procedure [4, 5].
However, Norwood-based palliation continues
to have significant early and interstage mortality in the current era with the majority of deaths
occurring in the peri-operative period after the
Norwood procedure [3, 6, 7]. After Stage I Norwood procedures, the presence of a systemicto-pulmonary shunt contributes to the intrinsic
instability of an in-parallel circulation in which
blood flow distribution may be altered significantly with perturbations in the ratio of systemic to pulmonary vascular resistance and this
vulnerability is compounded in the early postoperative period with post-cardioplegia related
depression of cardiac output. Cardiopulmonary
bypass (CPB) and deep hypothermic circulation
arrest (DHCA) contribute to a subsequent systemic inflammatory response which also has a
negative impact on the Norwood physiology in
the early postoperative period.

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Interstage mortality between Stage I and Stage

II palliation is also significant (10.5 - 22%) [3, 6]
and may be influenced by chronic volume loading of the systemic ventricle [8], arrhythmias and
shunt-related problems. These intrinsic problems with the Norwood strategy have encouraged the development of an alternative Hybrid
strategy.

Tel: 416-813-6420
Fax: 416-813-7984
E-mail: christopher.caldarone@
sickkids.ca

The hybrid palliative strategy has evolved rapidly in the last decade [9, 10] and is based on the
placement of bilateral pulmonary artery (PA)
bands, stenting of the ductus arteriosus, and
atrial septostomy as Stage I palliation during the
neonatal period, followed by arch reconstruction and bidirectional cavopulmonary shunt
as Stage II palliation at the age of four to six
months. Stage I hybrid procedures avoid CPB,
cardioplegic arrest, and CPB-associated postoperative systemic inflammatory response.
Furthermore, by deferring aortic arch reconstruction, the hybrid strategy avoids surgical
alterations in cerebral blood flow (DHCA and/
or regional cerebral perfusion) in the neonatal
period when the brain may be more susceptible
to neurologic injury [11]. Potential disadvantages of hybrid palliation include obstruction of
the aortic isthmus by stent deployment, subsequent coronary and cerebral malperfusion, and
mechanical distortion of the branch pulmonary
arteries.

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Several institutions have reported a significant learning curve with

the hybrid strategy [9, 12, 13] and we have recently reported measurable trends toward improvement in outcomes, suggesting that institutional learning is an important component in the development
of this strategy.

COMPARISON BETWEEN HYBRID AND

NORWOOD STRATEGIES
Early postoperative physiology after Stage I palliation
Pulmonary blood flow after Stage I palliation in Norwood and hybrid patients is derived from systemic-to-pulmonary artery shunts
with the objective of providing pulmonary blood flow which is sufficient for pulmonary gas exchange but controlled by the geometry
of the shunts/bands to prevent excessive volume loading of the
heart. In Norwood patients an aorto-pulmonary or a RV-PA shunt
is used, whereas in hybrid patients banding of the proximal branch
pulmonary arteries is used to control pulmonary blood flow.
The postoperative haemodynamics after first stage hybrid palliation have not been extensively studied. As the hybrid strategy has
evolved, avoidance of cardiopulmonary bypass was postulated to
better preserve myocardial function when compared to first stage
Norwood palliation. Using respiratory spectrometry, we compared
postoperative hemodynamics and oxygen delivery between Stage
I hybrid and Norwood patients and noted that the hybrid patients
had higher systemic vascular resistance (SVR) during the first postoperative 48 hours after the Stage I procedure [14].
This change was associated with lower cardiac output, low systemic
blood flow (Qs) and oxygen delivery. Interestingly, despite bilateral
PA banding, total pulmonary vascular resistance and pulmonary
blood flow (Qp) were not different between early postoperative
Hybrid and Norwood patients.

The ratio of pulmonary to systemic blood flow (Qp/Qs) after Stage

I Norwood palliation was between 0.3 and 3.3 (mean 1.20.5) and,
despite bilateral pulmonary artery banding, the Qp/Qs ranged
from 0.4 to 5.7 (mean 1.71.0) after Stage I Hybrid palliation[14].
However, in the absence of post-cardioplegia deficits in myocardial
performance, this level of overcirculation appears to be well tolerated in Hybrid patients with normal myocardial reserve. It is important to note, however, that this was an uncontrolled comparison
and the administration of vasodilators and inotropes was routinely
used for the Norwood patients [15] and uncommonly used for the
Hybrid patients. The noted differences between the groups may
have reflected the management strategy rather than differences in
the palliative strategies.
These data suggest that systemic afterload reduction such as milrinone and phenoxybenzamine may be important in the early postoperative period for post-Stage I Hybrid patients. Based on these
findings, we have adopted a low threshold to employ systemic
afterload reduction and inotropic support for neonates following
Hybrid Stage I procedures especially for those patients known to
have diminished preoperative myocardial reserve. We also recognize the potential for pulmonary overcirculation in patients with
diminished myocardial reserve and utilize standard intensive care
unit (ICU) measures to limit pulmonary blood flow in patients with
evidence of inadequate distal oxygen delivery.
Survival
Several centers initially reported high mortality after Stage I Hybrid
palliation [9, 13]. After a learning curve, outcomes tended to improve and were comparable with Norwood procedure in terms of
mortality. Hospital survival after Stage I Hybrid palliation has been
reported ranging from 80 to 97% in more recent studies [10, 16, 17],
although some studies excluded high-risk patients from the analysis. In our recent hybrid and Norwood experience (Figure 1) [18],
we performed 47 hybrid procedures between 2004 and December
2010.

Figure 1: Clinical outcomes of patients who underwent Hybrid or Norwood strategy. Tx; cardiac transplantation
(Citation from [18] with publishers permission)

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Figure 2: Kaplan-Meier survival analysis comparing Hybrid and

Norwood groups. There was no difference between the groups in 1
year survival. (Hybrid 68.5% vs. Norwood 64.3 %, p=0.88).

These hybrid patients consist of all neonates palliated with the

hybrid strategy excluding patients treated as a planned bridge to
cardiac transplantation or critically ill patients who underwent the
hybrid procedure as a salvage strategy. During the same period, the
Norwood procedure was performed in 63 patients.
There was no difference in mortality following Stage I palliation
between the groups (Figure 1). Freedom from death or transplant
after Stage II was comparable between two groups (Hybrid 88%vs.
Norwood 84%, p=0.95) [18]. There was no significant difference in
1 year overall survival between two groups (Hybrid 68.5% vs. Norwood 64.3 %, p=0.88, Figure 2).
Hemodynamics and pulmonary artery growth
Comparison of pre-Fontan catheterisation data between Hybrid
and Norwood procedures is shown in Table 1[18]. There were no
statistically significant differences in ventricular end-diastolic pressure and mixed venous saturation between the two groups. Mean
PA pressures are also equivalent between the groups. There was,
however, a non-significant trend toward larger Nakata index in the
Norwood group compared with the Hybrid group. Both groups had
equivalent PA growth and haemodynamics at the pre-Fontan catheterisation. These data suggest that the hybrid procedure leads to
comparable candidates for the Fontan procedure.

Table 1: Comparison in pre-Fontan hemodynamics, pulmonary artery growth and ventricular function between Hybrid and Norwood groups.

AVVR = atrioventricular regurgitation; EDP = end diastolic pressure;

LL = lower lobe; PA = pulmonary artery
AVVR: none/trivial=1, mild=2, moderate=3, severe=4
Ventricular function: normal=1, mild impairment=2, moderate=3, severe=4
(Citation from [18] with publishers permission )

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Ventricular function and atrioventricular valve regurgitation

Preservation of ventricular function and prevention of atrioventricular valve regurgitation (AVVR) are critical determinants in the
success of a single ventricle palliative strategy. These parameters
may be jeopardised at many points in the Norwood single ventricle
management strategy including:
1) myocardial ischemia-reperfusion injury after cardioplegic arrest
at Norwood Stage I palliation, 2) volume overloading of the systemic ventricle during the interstage period, and 3) impairment of the
right ventricular function due to ventriculotomy at the site of construction of RV-PA conduits in Norwood patients treated with the
Sano modification. On the other hand, the Hybrid procedure has
potential for diminished myocardial function due to potential for
restriction in coronary perfusion due to obstruction of retrograde
aortic arch flow through the aortic isthmus after ductal stenting.
The influence of the obstruction of retrograde
aortic arch on the Hybrid strategy
Obstruction of retrograde aortic arch flow in patients with diminished prograde aortic flow (e.g. aortic atresia) can be associated
with coronary and cerebral ischemia [19]. Obstruction can occur
during the Hybrid Stage I procedure immediately after ductal stent
deployment or the obstruction can develop in the interstage period due to progressive ingrowth of fibrous tissue as the site of intersection between the ductal stent and the aortic isthmus [13, 19, 20].
Stoica et al. described a treatment strategy for patients with retrograde aortic arch malperfusion based upon surveillance, detection, and catheter-based treatment including retrograde stenting
of the aortic isthmus in the subset of patients in whom surveillance
resulted in detection of the stenosis. The strategy was associated
with a high incidence of death or transplantation among patients
in whom retrograde aortic arch obstruction was treated suggesting that a treatment strategy may not be the optimal management
plan for addressing retrograde aortic arch obstruction [19]. Because
of the lack of success with a treatment strategy, the authors favour
the Norwood strategy for patients who are considered at risk for
retrograde aortic arch obstruction.
As an alternative to a treatment-based strategy, we have developed
a preventative strategy to address potential for retrograde aortic
arch obstruction in Hybrid patients. In this strategy, we utilise the
creation of prophylactic reverse Blalock-Taussig (BT) shunts for
patients with restricted antegrade aortic flow and potential retrograde aortic arch obstruction [21]. Importantly, we have not needed
to utilise retrograde stenting of the aortic isthmus as a treatment
for arch malperfusion in any of the patients with a prophylactic reverse BT shunt. The reverse BT shunt may have helped to neutralise
the risk of retrograde aortic arch obstruction. Because we have not
detected a significant survival disadvantage in the high-risk subset of patients with severely diminished prograde arch flow, we are
continuing to utilise the reverse BT shunt as a prophylactic component of our hybrid management strategy in this high- risk group.
Ventricular function and AVVR were not different in a comparison
of the hybrid and Norwood groups at the pre-Fontan evaluation
as shown in Table 1 (p-value = 0.7 and 0.27 respectively) [18]. These
data indicate that the Hybrid strategy has equivalent results with
Norwood strategy in terms of preservation of ventricular function
and atrioventricular valve function.

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Influence upon neurological development

Neurological development is a major concern with any treatment
strategy for single ventricle palliation. The mean neurocognitive
test results in school-aged children with HLHS who underwent the
Norwood procedure or cardiac transplantation are significantly
below population normative values [22]. In addition, pre-operative
brain magnetic resonance imaging revealed that brains of HLHS
patients are smaller and less mature before surgery than patients
without congenital heart disease [23]. Thus, the impact on neurological development is of critical importance for the single ventricle
strategies.
The Hybrid strategy has a potential advantage in terms of preservation of neurologic function in comparison to the Norwood strategy.
By delaying aortic arch reconstruction until the second stage procedure at four-six months of age for Hybrid patients, there is indirect
evidence suggesting that the delay may have a favorable impact on
the neurological development. Galli et al reported that the development of periventricular leukomalacia (PVL) after cardiac surgery
is more prevalent in neonates compared with those at the age of
more than one month [11] suggesting age-related vulnerability to
neurologic injury. PVL in preterm infants is associated with subsequent cerebral palsy, mental retardation, and learning disabilities.
Thus, there is an age-dependent window of vulnerability to brain
injury [11] and the Hybrid strategy may have an advantage in delaying aortic arch reconstruction from the neonatal period to four-six
months of age. Objective demonstration of this advantage, however, will require a controlled clinical trial.
In contrast to the age-related potential neurological advantage of
the Hybrid strategy, there is a potential disadvantage with the Hybrid strategy. As mentioned above, the obstruction of retrograde
aortic arch flow can limit cerebral blood flow for four to six months
prior to arch reconstruction at the Stage II procedure and long periods of limited cerebral blood flow may be detrimental to neurologic development. If the reverse BT shunt can successfully maintain
arch perfusion, it may neutralise this problem. Further long term
neurologic evaluation is required to compare the Norwood and Hybrid strategies in the context of neurologic function.
Intubation time, intensive care unit stay and hospital stay

Another potential benefit of Hybrid procedure is that Hybrid patients have shorter total intubation time, ICU stay, and hospital
length of stay (combined Stage I and II among survivors) [17, 24].
Galantowicz et al. reported that 85% of Hybrid patients at both
Stage I and II were extubated in the first 24 hours [16]. Interestingly,
in our experience, we have noted a time-related tendency toward
improvement in the intubation time, the length of ICU stay, and
hospital stay at the Hybrid Stage II, while concurrent Norwood patients did not have evidence of time-related improvements in these
parameters suggesting that we had reached a plateau in terms of
refinement of the Norwood strategy [17].
Although there is less consumption of conventional measures of resource utilisation including intubation time, ICU stay, and hospital
length of stay in Hybrid strategy, unplanned reinterventions were
more frequent in the Hybrid patients compared with the Norwood
patients [18] (Hybrid 31.3% vs. Norwood 9.3%, p=0.016, Figure 3).
Any comparison of resource utilisation must include quantification
of planned and unplanned hospital admissions, procedures and
interventions. Therefore, we are currently undertaking a study to
examine total resource utilisation in a comparison of two palliative
strategies.

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Figure 3: Freedom from unplanned reintervention after Stage II between Hybrid and Norwood groups at 3 years.
Unplanned reintervention rate was higher in Hybrid group compared to Norwood group (31.3% vs. 9.3%, p=0.016).
This data does not include unplanned reinterventions prior to Stage II (Citation from [18] with publishers permission).

CONCLUSIONS

2. Which strategy produces the better Fontan candidate?

Hybrid palliation is an evolving surgical strategy with comparable

survival to reported Norwood-based series. The Hybrid strategy
provides equivalent pre-Fontan haemodynamics and pulmonary
artery growth, preserves ventricular and atrioventricular valve
function, and reduces resource utilisation. The comparative impact
of the two different surgical strategies on neurological outcome is
not defined and should be a subject of prospective trials.

The Fontan procedure represents the convergence point for both

management strategies. Parameters for this comparison include
haemodynamics, ventricular function, valvular competence and
pulmonary artery growth.

FUTURE DIRECTIONS

If all other factors are equal, the superior strategy is the one that
utilizes the least resources and poses the smallest burden on institutions and families.

Important questions to frame comparisons of the Hybrid and Norwood strategies include:
1. Which strategy is associated with better long term
neurodevelopmental outcomes?

3. Which strategy is associated with the most efficient use of

resources when quantifying the entire resource burden from
birth to Fontan procedure?

Based on demonstration of equivalent survival, a prospective

randomised trial should be undertaken to compare the Norwood
and Hybrid strategies in the context of these three fundamental
questions.

There are compelling arguments for and against each strategy. In

the past, the timing of arch intervention was immutable and hypoplastic aortic arches required repair in the neonatal period. With
the Hybrid strategy, it is now possible to defer aortic arch reconstruction and test the hypothesis that age is an important mediator
of the vulnerability to injury after aortic arch reconstruction.

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