A REVIEW OF HEMODYNAMICS BEHIND HYPOPLASTIC LEFT HEART SYNDROME

1. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
1
A review of hemodynamics behind
Hypoplastic left heart syndrome
Guzmán S, Dayana*
*
dlguzmans@ua.pt
Abstract
Congenital heart defects are a group of structural problems in which the Hypoplastic left heart
syndrome affects 0.16 in each 1000 neonates, although this disease is one of the main responsible
of deaths in first weeks of birth. Along the years a palliative procedure of three stages to HLHS has
been made and modified to improve the body’s response, the hemodynamics analysis allowed the
design and assessment of those changes, as well as the approaching of this concepts in
computational simulation have increased the possibilities to novel realistic proposals for less
invasive methodologies, grafts modifications and new corrective devices and assist systems. In this
document an attempt to give general view about the methods and devices used for the HLHS
treatment was done.
Key words
Hypoplastic left heart syndrome, Norwood, Glenn, Fontan, grafts, hemodynamics.
Introduction
The Hypoplastic left heart syndrome (HLHS) is the cause of the 1.5% of congenital heart defects in
the world and is the responsible of the 25% of deaths caused by congenital cardiac problems in
the first week after birth.1
It is characterized for the presence of a group of structural defects and
mainly the under development of the left side of the heart specially the total or partial absence of
the left ventricle which implies a lack in the blood flow and an instability in the systemic
circulation1–3
.
The treatment consist in the development of three palliative procedures (Norwood, Glenn y
Fontan) which take place in the first 4 years of the patient, other option is to make a total heart
transplantation but this is not viable because of the limit of donors availability1,4–6
.The interstage
survival vary from 70% to 95% in the last years, being the first stage crucial in the normalization of
the hemodynamic variables7
. For each procedure there have been done various modifications in
terms of methods and devices, these contributions have allowed the definition of more effective
and less invasive protocols, the reduction of other heart diseases development risks and the
raising on the life expectancy, nevertheless the great surgical component has opened the
discussion on the proposal of new paradigms searching for the new protocols and methods
designs to correct the defect instead of adapt to them8
.

2. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
2
In this document a general revision have been done, considering the main palliative procedures
modifications for the treatment of the HLHS, taking in account the principal hemodynamic factors
in the design of grafts which are used in each procedure, additionally the current investigations
related to a paradigm shift are presented, showing the possible applications of biomedical
materials and devices sciences.
Background
Heart structure and blood circulation
The heart contains four chambers (Figure 1): the left and right atria which are separated by an
interatrial septum and receive venous blood, and the left and right ventricles which pump the
blood into the arteries and are also divided by an interventricular septum.9
Figure 1. Heart structure.
In the normal cardiovascular system the oxygen-poor blood (“blue”) that flows through the upper
and lower body enters the right atrium (RA) from the superior vena cava (SVC) and the inferior
vena cava (IVC), then passes through the tricuspid valve to the right ventricle (RV) which pumps
the blood to the pulmonary artery (PA) through the pulmonary semilunar valve to the lungs,
ended the pulmonary circulation, the systemic circulation takes places by receiving the oxygen-
rich blood(“red”) that flows through the pulmonary veins, in the left atrium(LA), blood passes
through the mitral valve to the left ventricle (LV) which pumps the blood to the Aorta through the
aortic semilunar valve, in the aorta the blood is delivered to the rest of the body.10
Before birth the resistance in the fetal pulmonary circulation is very high, therefor, the heart
doesn’t send blood to the lungs to get oxygen and all the oxygen the baby needs passes from the
mother’s blood to the baby through the placenta and umbilical cord. In this stage of the cardiac
development there is an opening in the interatrial septum called foramen ovale allowing the

3. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
3
blood to pass from the right atrium to the left part of the heart, and a second shunt that transfers
most of the pumped blood from the pulmonary artery and the aorta called ductus arteriosus
(Figure 2). these extra openings allow oxygen-rich blood to bypass the baby´s lung and still
circulate through the body. Normally, within a day or two after birth both the ductus arteriosus
and the foramen ovale close, forcing the baby blood to travel to the lungs to pick up oxygen11,12
.
Figure 2. Circulation in fetus and newborn
Hypoplastic left heart syndrome.
The congenital heart defects are a group of structural problems of the heart where the organ is
not well developed, this diseases are divided in non-cyanotic and cyanotic defects depending on
the way the blood flow, cyanosis implicate bluish skin as consequence of poor and rich oxygen
blood.

4. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
4
The HLHS is one of the cyanotic congenital heart defects, it is related to a significant
underdevelopment of the left side of the heart, mainly the left ventricle, it is normally
accompanied by other structural defects which include coarctation of the aorta, interatrial
anastomose or the presence of the foramen oval (Atrial septum defect) and the non-closure of the
ductus arteriosus (Figure 3), the existence of last two defects are necessary to maintain the baby
alive otherwise the system would be unsustainable with fatal consequences, as a result, the right
heart must be in charge of systemic circulation13
.
Figure 3. HLHS heart
In the Hypoplastic heart the poor-oxygen blood flows from the SVC and IVC to the right atrium,
pass through the tricuspid valve to the right ventricle and is pumped to the lungs through the
pulmonary trunk, in the systemic circulation, the rich-oxygen blood pass through the foramen oval
due to the inexistence of the ventricle going through the tricuspid valve again to the right
ventricle, some blood goes through the ductus arteriosus to the aorta and is delivered to the rest
of the body, the cyanosis is the result of the mixture of rich and poor-oxygen blood since it flows
to the right atrium(Figure 4).1,2
The diagnosis techniques allow the identification of these heart
defects before birth, however the design of the operation methods are applicable only at neonate.
Figure 4. HLHS circulation

5. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
5
Hemodynamic parameters
The effectiveness of the procedures can be assessed by the measure of the hemodynamic
parameters, the main values for the HLHS procedures are the cardiac output(CO)[mmHg] the
arterial Blood Pressure [mmHg], the Mean Arterial Pressure(MAP)[mmHg], the stroke volume
variation[%], the pressure in right and left chambers[mmHg], de systemic and pulmonary vascular
resistance[dynes*s/cm3
], the diastolic and systolic ventricular volumes[ml] and the oxygenation
parameters14
.
Some of the main equations are presented below 10
:
Where, RAP is the right atrial pressure and TPR, the total peripheral resistance.
MAP (2)
Where the pressure drop gradient, µ is is the viscosity, the length of the tube, Q is the flow
rate of the blood in the vessel and r the radius of the vessel.
The Navier-Stoke equation is frequently used to simulate the blood motion in vessels:
(4)
Represents the relation among the velocity, the pressure, the density, the viscosity and the time,
the blood is assumed as a Newtonian fluid due to the large sizes of vessels in comparison with a
blood cells size15
.
Palliative procedures: from past to current applications
Since the decade of 80´s a series of palliative procedures have been developed, although, they do
not correct the defect, allows the adaptation of the heart to a new functioning way to extend the
life expectancy of the patient until it could receive a new heart, the objectives of these operations
enclose the cyanosis elimination and the normalization of the main hemodynamic variable as
cardiac output, blood pressure, atrial resistance and oxygen saturation. The first stage is called
“the Norwood procedure” and takes place in the first week of birth, in this procedure the blood
flow through the aorta is increased, the pulmonary blood flow is reestablished using a systemic
pulmonary shortcut that is a tubular mechanic device made of polytetrafluorethylene (PTFE) of 3
to 5 mm 5,16,17,15
, an atrial septoctomy is made (total opening of the foramen oval)as well, six
months later the Glenn procedure is made, the objective of this operation is to decrease the effort

6. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
6
in the right ventricle by the anastomose of the SVC and the right pulmonary artery, finally, from
age of eighteen months to three years, the Fontan operation take place by the shunt of the IVC to
the left pulmonary artery, in this stage the cyanosis is completely eliminated and the right heart is
responsible of just the systemic circulation2
.
Figure 5. Example of lumped parameter model applied to shunts.
16
Over the years several modifications to each stage have been done, the approaching of
computational fluid dynamics software and other available simulation resources permit the
assessment of different kinds of grafts for design.
In relation to the first stage there are three main procedure modification, In the original Norwood
technique a Blalock-Taussing shunt is used to connect the pulmonary trunk to the subclavian
branch of the aorta18
, the high percentage in mortality after classical Norwood procedure brought
a new proposal where the graft is used to generate de anastomose of the right ventricle and the
pulmonary artery (RV-PA) giving a unique path for the blood to pass to the lungs(Figure 6)19
,
Reinhartz et al. proposed a valved RV-PA modification that improve the blood flow and increasing
the life expectancy20
, these two last modifications showed a pulse pressure decrease, an stable
pulmonary to systemic ratio (Qp/Qs), lower systolic and diastolic pressures in the right ventricle
performance, and an increasing in coronary perfusion pressure. The RV-PA graft flow is presented
mainly in systole which helps in the diminution of possible diastolic regurgitation; it also
demonstrated a higher mechanical efficiency and minimal stroke work16
. A Ring-Reinforced RV-PA
was proposed by Baird et al. with the objective of decrease the interstagial extra procedures21
,
another less invasive modification called hybrid procedure is proposed, in this operation the
aortic flow is augmented by the use of an stent inserted with catheterization in the pulmonary
trunk and the coarctation of the pulmonary left and right arteries, this procedure cause the
expansion of the aorta to increase the blood flow through it22
.

7. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
7
Figure 6. Systemic to pulmonary shunts, A) Classical procedure Blalock-Taussing, B &C) RV-PA modifications
At the end of the Norwood procedure de stabilization of the arterial pressure is obtained(Figure 7)
23
. Using the equation to calculate the main arterial pressure the main arterial pressure (MAP) =
49.9 mmHg, this value is in the ranks of the normal heart functioning pediatrics standar24
.
Figure 7. Pressure values before Norwood procedure
Since the ending of the 90’s decade the Glenn procedure starts to be used as an important stage in
the success of the palliative procedure, this technique refers to an upper cavopulmonary
anastomose, investigations demonstrated that the application of this operation before the Fontan
technique considerable decreased the interstagial mortality rate25
. There are two methodologies
for the second stage, the bidirectional Glenn procedure (BDG) and the hemifontan procedure
(HFP) (Figure 8). The development in computational analysis techniques has allowed an
approaching to the possible results, Bove et al. demonstrated that , although, the HFP presents

8. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
8
lower power losses there is not a fundamental difference while the values of hemodynamic
variable are compared in both operations(Figure 9)26
.
Figure 8.3D grafts , A)HMF model, B) BDG model
Figure 9. Some hemodynamics parameters to compare both Glenn devices.
In the last stage called Fontan procedure the IVC is shunted to the left pulmonary artery, several
grafts variations of intra and extra-cardiac have been designed, the modifications depends on the
previous Glenn type procedure, therefor, after the hemifontan procedure a selected graft called
total cavopulmonary conduit is used (TCPC) and after the BDG procedure the graft is related to
and extra cardiac conduit (ECC) that is placed out of the heart in contrast to the prior conduit, that
is located inside the right atrium (Figure 10); the power losses were lower in the TCPC devices26
. In
the next decade Trusty et al. lead a cohort study where the hemodynamic variables of grafts used
in sixty patients were assessed. The main characteristic was the structure design of commercial
grafts, showing a bifurcation in the top extreme (Y-graft) which is connected to the pulmonary
artery, they also compared the TCPC with an ECC group of Y-graft to demonstrate that the results
were independent of the graft localization. The graft shape allows the resistance and arterial
pressure control but the bifurcation is not the best model due to the high increase in pressure by
the Y section, this study was useful to make a call for new graft sketch development for the Fontan
procedure27
.

9. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
9
Figure 10. Fontan procedures intra and extra cardiac
After all these modifications, simulations and studies, the Norwood three stage procedure is
getting obsolete, this fact opened the investigation to a new proposal to replace the current
procedure or at less some of the stages, s works have been presented, Honjo O. et al. presented a
primary “in-series” palliation in neonates with Hypoplastic heart syndrome, with two mechanical
assist devices the hemodynamic parameters in assessment were the blood gas values and the
arterial SaO2(Figure 11)28
. Other ventricular assist devices have been presented in consequence of
high number of Fontan failure cases, this devices are implanted in the patient body and act to
stabilize the hemodynamics parameters(Figure 12)29–31
; there are also devices to decrease the
invasive processes y second a third stages 32
, Additionally, Patel et al. presented their work in the
design and fabrication of a bioengineered open ventricle, this project suggest the approaching of
the new technologies in tissue engineering to repair the heart instead of a surgical
procedure(Figure 13)33
.
Figure 11. A) SVC-to-PA pump assist, B)SVC-RA oxygenation assist

10. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
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Figure 12. Artificial ventricle
Figure 13. First steps of bioengineered ventricle fabrication.
Conclusion
The development of effective procedures and devices for the HLHS treatment is one of the great
challenges of bioengineering and biomedicine in the current time. In this narrative review, general
information about methods and devices for the palliative treatment of HLHS was done, pointing
out the main sources where the hemodynamics assessments have been made. In addition the
importance of the biomaterials and devices sciences for novel proposal to the necessity of
corrective operations instead of palliative ones is deducible. Finally, the hemodynamic parameters
analysis allows the simulation of processes to advance in the design and evaluation of possible
novel devices in real patients.

11. Human biophysics, Master in Biomedical materials and devices, Universidade de Aveiro.
11
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