++
Single ventricle or univentricular heart
refers to a limited number of congenital heart lesions from a strict
anatomic perspective. Anatomically, single ventricle lesions can
be either a single left ventricle, due to agenesis of the right
ventricular inlet (there is often a small component of the right
ventricular outlet present), or a single right ventricle, secondary
to agenesis of the left ventricle.1,2 In both,
the atria drain through one or two atrioventricular valves into
the only ventricular chamber (Fig. 498-1).
These lesions are rare, and do not include common lesions such as
tricuspid atresia and hypoplastic left-heart syndrome.
++
++
In practice the concept of “single ventricle” expands
beyond the strict anatomic definition, and refers to all congenital
heart lesions that share a single ventricle physiology, regardless
of the underlying structural variant.3,4 This expanded
functional definition includes all those lesions in which the patient
lacks a second ventricle that can independently support the pulmonary
circulation. In most such lesions, components of a second ventricle
exist.
++
In single ventricle physiology the circulations mix at the atrial
and/or ventricular level. The surgical approach typically
consists of various staging procedures which result in a complete
separation, or “bypass,” of the pulmonary circulation
from the heart. The final surgical stage that fully separates the
pulmonary circulation is known as the modified Fontan operation.
The “single ventricle” then becomes the systemic
pumping chamber, and the systemic venous return flows passively through
the pulmonary circulation without interposition of a ventricular
pump.3
++
Thus, the single ventricle from a physiologic perspective includes patients
with
++
- single right ventricle
- single left ventricle
- unbalanced complete atrioventricular (AV) canal (a common
AV valve is more aligned to one ventricle than the other, typically
associated with asymmetry in the development of the two ventricular
chambers)
- tricuspid atresia (eFig. 498.1)
- hypoplastic tricsupid valve and right ventricle, frequently
with intact ventricular septum and pulmonary atresia
- mitral atresia
- hypoplastic left heart syndrome and its variants (eFig. 498.2)
++
In addition, single ventricle physiology also exists in patients
with complex intracardiac anatomy such that surgical septation of
the ventricles cannot be performed, thus, they are managed in the
same pathway as those with more traditional forms of single ventricle physiology.
Examples are double outlet right ventricle and straddling atrioventricular
valves, noncommitted ventricular septal defects, and complex multiple ventricular
septal defects, for which surgical septation is not feasible. In
such patients, following a Fontan procedure, two ventricles function
together as the systemic ventricle.
++
++
++
Within the group of patients with heterotaxy (variable and often
discordant situs of the viscera and cardiac segments), single ventricle variants
are frequent, especially in the asplenia group (right atrial isomerism),
in which a common atrioventricular valve drains into a main ventricle,
with hypoplasia of a secondary ventricle. D-malposition of the aorta,
severe stenosis or atresia of the pulmonary outflow tract, and anomalous
pulmonary venous connections are frequent associated findings.5
++
Single ventricle physiology is an evolutionary step backward.
The right ventricle appeared in reptiles and birds 165 million years
ago to allow adaptation to air breathing, aerobic exercise, and
flying. Patients with single ventricle physiology therefore lack
an important mechanism of adaptation to aerobic exercise, so that
exercise limitation is frequent in this group of patients, even
after the final surgical palliation.6
++
Utilizing the segmental approach, each anatomic level can be
analyzed.7-10
++
1. Atria: solitus, inversus, or ambiguous (heterotaxy).
The situs of the atria typically coincides with the situs of the
viscera (if there is situs inversus of the viscera and the stomach
is on the right side, then it is likely that the right atrium will
also be inverted, on the left side). In solitus, the right atrium
is right sided, receiving the systemic venous return, whereas the
left atrium is left sided. When there is neither situs solitus nor
inversus, the patient is said to have situs ambiguus.
2. Atrioventricular connections: In addition to normal atrioventricular connections,
there may be double-inlet connections in which the mitral and tricuspid
valves enter a single ventricle, a common inlet (complete common
atrioventricular valve), or atresia of the mitral or tricuspid valve.
3. Ventricles: The ventricles may have a normal D-loop, in which the
right ventricle is to the right of the left ventricle or an L-loop,
in which the right ventricle is to the left of the left ventricle.
4. Conotruncus or outflow: The normal relationship of the aorta
to the pulmonary artery is rightward, lower, and posterior, with
fibrous continuity of the aortic valve with the atrioventricular
valves. The D-malposed aorta is anterior and to the right of the
pulmonary artery, whereas the L-malposed aorta is anterior and to
the left of the pulmonary artery
++
The normal segmental description of situs solitus based upon
the above considerations is {S,D,S}. Many different
segmental combinations can be found in single ventricles. Among
the “anatomic” single ventricles, single left
ventricle is more common2,10 (eFig.
498.3), with the vast majority having an infundibular outlet
chamber and discordant ventriculoarterial connections (transposition).
Inverted ventricular loop (L-loop) with transposition and left outlet
chamber is slightly more frequent than ventricular D-loop. A small
percentage has normally related great vessels, with a right sided
infundibular outlet chamber (Holmes heart) ({S,D,S}).11
++
++
In addition to this segmental description, the presence or absence
of obstruction at any level within the heart or great arteries is
determined (eTable 498.1). For example, in
double inlet left ventricle, the opening between the left ventricle
and the hypoplastic right ventricular outflow chamber may be restrictive.
This causes subaortic obstruction in the setting of transposition,
or subpulmonary stenosis if the vessels are not transposed (Holmes
heart). Coarctation of the aorta is often present in those patients
with subaortic obstruction.
++
++
Overall, patients with single ventricle preoperatively tend to
have complete mixing of pulmonary and systemic venous returns within
the heart (Fig. 498-2). Blood leaving the
heart goes both to the pulmonary and systemic circulations; therefore,
the aortic and pulmonary oxygen saturations are usually equal but sometimes
streaming of blood within the heart causes differences in aortic
and pulmonary oxygen saturations. The single ventricle is volume
overloaded, as it supplies both circulations. This parallel circulation
is relatively inefficient because some previously oxygenated blood
from the lungs returns to the pulmonary circulation and some systemic
venous blood is shunted into the systemic arterial circulation (Fig. 498-2, eFig. 498.4).3
++
++
++
The
balance between the systemic and the pulmonary circulations depends
on multiple factors, including anatomic obstruction as well as relative
vascular resistances and perfusion pressure.Assuming no lung disease,
and a constant arteriovenous oxygen difference, based on the systemic
oxygen saturation, one can estimate the Qp/Qs,
or relationship between the pulmonary and systemic blood flows (eFig. 498.5). Ideally, the (Qp/Qs)
should be kept at least at 1:1, which typically is achieved in the presence
of complete mixing when the systemic arterial oxygen saturation
is around 75%, in the absence of lung disease and with
a normal cardiac output. Some cardiologists recommend maintaining
aortic oxygen saturation over 85% with a QP/QS of
1.5 to 2, to improve growth potential.
++
++
Qp/Qs can be calculated by the simplified
formula
+
++
where Spv is the hemoglobin oxygen saturation of blood
in the pulmonary veins, Spa is the saturation in the pulmonary artery, Ssa is
the saturation in the systemic artery, and Ssv is the mixed
saturation in the systemic veins.
++
In the absence of obstruction at any level, the relationship
between pulmonary and systemic blood flow depends on the relative
resistances of the two vascular beds. At birth, Qp/Qs is
only modestly increased as pulmonary vascular resistance falls from
in utero levels, so that systemic arterial oxygen saturation is generally
in the mid 70s. As pulmonary vascular resistance decreases in the
first few weeks of life, pulmonary blood flow and systemic arterial
oxgyen saturation increase greatly because the vascular resistance
of the pulmonary vascular bed is much lower than that of the systemic
bed. Saturations greater than 85% are associated with such
high pulmonary blood flow and in some of these patients heart failure
may develop, with respiratory distress, diaphoresis, and failure
to thrive. Providing supplemental oxygen to infants with single
ventricle to increase saturations when the oxygen levels are above
80% can be detrimental, as oxygen acts as a pulmonary vasodilator,
decreasing pulmonary vascular resistance, increasing the pulmonary
blood flow, altering the Qp/Qs relationship
such that the systemic output decreases.3
++
However, many patients with single ventricle physiology have
various levels of obstruction within the heart and great vessels,
so that Qp/Qs depends on factors other
than relative vascular resistances. The levels of obstruction include
++
- Pulmonary or subpulmonary stenosis or atresia: This may
lead to a marked decrease in systemic arterial oxygen saturation,
as the ductus arteriosus closes over the first hours of life. The
degree of cyanosis is determined by the severity of the obstruction.
In patients with severe pulmonary stenosis or pulmonary atresia,
severe cyanosis can occur rapidly, and is a life-threatening event.
In that situation, the infant is considered to be “ductal
dependent.” Prostaglandin E1 is started immediately
to reverse the problem. The typical hemodynamic status once the
PDA is opened is illustrated in eFigure 498.6.
++
++
- Systemic (aortic) obstruction: This can be below the aortic
valve (subaortic stenosis), at the valve, in the aortic arch (hypoplasia
or aortic arch interruption), or in the aortic isthmus between the
left subclavian artery and ductus arteriosus (coarctation of the
aorta). When the obstruction is critical, newborns are ductal dependent,
meaning that patency of the ductus arteriosus is necessary to maintain adequate
systemic blood flow.
- Atrioventricular obstruction: With a stenotic or atretic atrioventricular
valve, restriction of flow between the two atria can be very deleterious.
In the hypoplastic left heart syndrome, for example, restriction
at the foramen ovale causes severe left atrial and pulmonary venous
hypertension. Severe pulmonary edema necessitates an emergency intervention
to decompress the left atrium. This is done either via a balloon
atrial septostomy, or more commonly now, placement of an interatrial
stent. Restriction across the atrial septum is less common in right
sided lesions but it can occur. If it does, the patient presents
with low cardiac output and systemic venous hypertension.
++
The vast majority of the patients with single ventricle variants
develop symptoms in the newborn period and early infancy. Patients
with ductal dependent lesions need emergency intervention. Those
with increased pulmonary blood flow may show signs of heart failure
as the pulmonary vascular resistance drops, whereas those with decreased
pulmonary blood flow have severe cyanosis. If not treated, death
occurs in infancy in more than 50% of patients,12-14 more
than half occurring during the neonatal period.
++
Patients with increased pulmonary blood flow may develop irreversible
pulmonary vascular changes after the first year of life, leading
to a decrease in the Qp/Qs. As pulmonary
blood flow decreases the symptoms of heart failure resolve, but
progressively severe cyanosis appears. Typical complicating features
related to cyanosis and polycythemia include stroke, renal dysfunction, scoliosis,
and endocarditis. Patients eventually develop progressive ventricular
dysfunction, arrhythmias, and worsening heart failure.
++
Most adult survivors without intervention are those with a systemic left
ventricle with 2 well-functioning atrioventricular valves, situs solitus,
and pulmonary stenosis of moderate degree, protecting the pulmonary
bed and no subaortic or aortic obstruction. Approximately a quarter
will have developed pulmonary hypertension with various levels of
vascular hypertensive pulmonary arteriopathy. Most survivors have
signs of congestive heart failure. Complete heart block can develop
in patients with discordant ventricular loop {S,L,L}variants,
requiring a pacemaker.13 Progressive insufficiency
of the atrioventricular valves is poorly tolerated in patients with
single ventricle, especially with a single or dominant right ventricle.
Patients with heterotaxy have a worse prognosis, due to the frequency
of severe pulmonary stenosis or atresia, or to a dominant anatomically
right ventricle and associated insufficiency of the atrioventricular
valves, which can predispose to the development of ventricular dysfunction.15
++
Patients with single ventricle have variable physical examinations, depending
on the presence or absence of associated pathology, particularly
pulmonary or systemic obstruction.15
++
- Pulmonary stenosis (decreased pulmonary blood flow): Variable
cyanosis is present. Patients with significant pulmonary stenosis develop
similar clinical manifestations as patients with tetralogy of Fallot,
and cyanosis will be the most remarkable feature on examination.
Patients with mild stenosis may be acyanotic. As patients get older,
clubbing becomes evident. Patients rarely have thoracic deformities.
Their precordium is commonly normoactive. There may be a left superior
parasternal palpable lift in patients with l-transposition. The
peripheral pulses are usually normal. On auscultation, there is
a systolic ejection murmur of intensity and duration directly correlating
with the amount of pulmonary blood flow, and inversely correlated
with the severity of the pulmonary stenosis and level of cyanosis.
The absence of a systolic ejection murmur may suggest pulmonary
stenosis. A continuous murmur from a patent ductus or aortopulmonary
collateral vessels may be present. The second heart sound is commonly
loud and single (aortic component), particularly in the patients
with l-transposition.
- No pulmonary stenosis (increased pulmonary blood flow): With
no pulmonary stenosis, patients tend to present with heart failure due
to increased pulmonary blood flow, manifested by respiratory distress,
diaphoresis, and poor weight gain. Cyanosis is minimal or absent.
Patients more commonly have thoracic deformities and a hyperdynamic
precordium. A soft systolic ejection murmur in the midprecordium
with radiation to the axilla and to the back represents relative
pulmonary stenosis. The second heart sound is loud, in the base, with
simultaneous aortic and pulmonary components. An S3 gallop and a
mitral valve middiastolic rumble can be auscultated in the apex.
- Systemic outflow or aortic obstruction: In newborns, systemic
obstruction presents typically with signs
of hypoperfusion, including decreased peripheral pulses, duskiness,
and, eventually, cardiovascular collapse. Findings specific to the
level of obstruction may be found, particularly in the older infant
with adequate systemic output. When a systolic thrill in the base
and suprasternal notch appears, subaortic stenosis should be suspected.
On auscultation, there is a harsh, loud systolic ejection murmur
in the base and mid precordium with radiation to the neck. When
the obstruction is valvar, a prominent systolic ejection click is audible
in the retrosternal area. When coarctation of aorta is present,
the peripheral pulses and blood pressures are unequal.
- Pulmonary venous obstruction: The presence of more severe
pulmonary edema and congestion than expected from the amount of pulmonary
blood flow or ventricular dysfunction suggests severe obstruction
of the left atrioventricular valve with a restrictive atrial septal
defect, or anomalous pulmonary venous connections with obstruction,
the latter particularly common in patients with heterotaxy syndromes.
++
The signs of chronic cyanosis and polycythemia are obvious in
older palliated patients but tend to be subtle in the infant and
young child. As surgical staged palliation leads to near normalization
of oxygen saturations, the detrimental effects of chronic cyanosis
are rarely seen in patients with single ventricle nowadays, except
for those who are not good candidates for palliation or who have
failed the procedures already.
++
Following surgical palliation cardiac examination depends on
the procedure performed and the underlying anatomy. An aortopulmonary
shunt is associated with a continuous murmur at the site of the
shunt. The second heart sound is single after a modified Norwood procedure.16 Murmurs
are frequently absent after the bidirectional Glenn and modified
Fontan procedures, A blowing systolic murmur occurs in the setting
of systemic atrioventricular valve regurgitation, whereas a systolic
ejection murmur may indicate subvalvar or valvar aortic stenosis,
or anterograde flow across the pulmonary valve into the pulmonary
arteries in certain anatomic variants. A diastolic murmur is typically
due to semilunar valve regurgitation (which happens quite commonly
in patients in whom the anatomic pulmonary valve becomes the neoaortic
valve after a Norwood palliation).
++
During evaluation and follow-up, patients with single ventricle
variants regularly undergo an electrocardiogram, echocardiogram, chest
x-ray, and pulse oximetry. The results vary depending on the underlying
anatomic variant. Some electrocardiographic and radiographic findings
are pathognomonic of the condition. When children are over 7 years
of age, cardiopulmonary stress testing is also performed. Holter
monitors are obtained every other year to evaluate the presence
of silent arrhythmias. Cardiac magnetic resonance is ordered more
and more often to evaluate anatomic and functional features in these
patients. Cardiac catheterization continues to be generally performed prior
to surgical procedures, and it is especially indicated when complications
arise during follow-up with possible interventional transcatheter
therapy to address specific abnormalities encountered (Table
498-1).
++
++
The electrocardiographic findings are very variable in single
ventricle patients, and depend on the underlying anatomy. Occasionally they
may be pathognomonic. For example, patients with tricuspid atresia
frequently have a superior axis with counterclockwise loop and decreased
right ventricular forces. Ventricular inversion is indicated by
inverted initial activation with Q waves in the right precordial
leads (qRS or qR in V1) in association with the absence of Q waves
in the left precordial leads (RS in V6). This is important to appreciate
because such patients are at risk of developing complete atrioventricular
block over time.13
++
Patients with hypoplastic left ventricle show diminished left
ventricular forces and dominant right-sided forces, but this may
be subtle enough that it is indistinguishable from the normal newborn
electrocardiogram (ECG). Unlike the normal newborn, the right ventricular
hypertrophy persists and is often associated with ST-T wave changes,
reflecting strain pattern (eFig. 498.7).
Patients with hypoplastic right heart variants such as pulmonary atresia
with intact ventricular septum show diminished right-sided forces,
with relative left-axis deviation for a newborn. Ischemic changes
can also be present in those patients who have this condition associated
with severe coronary abnormalities. Patients with single right ventricle
have signs of right ventricular hypertrophy. With unbalanced ventricles
there typically is an underlying endocardial cushion defect, there
is an associated left anterior hemiblock pattern with signs of left
ventricular hypertrophy when the left ventricle is dominant, or
right ventricular hypertrophy if the right ventricle is dominant.
++
++
Chest x-ray findings also vary considerably with variations in
the anatomy of single ventricle patients, as noted below.13,14
++
In patients with pulmonary stenosis the cardiac silhouette is
of normal size and there are diminished pulmonary vascular markings.
In the absence of pulmonary stenosis there is usually cardiomegaly
and increased pulmonary vascular markings, either due to high flow (increased
active vascularity) or pulmonary venous congestion (increased passive
vascularity).
++
With abnormal ventricular looping and ventriculoarterial relationships,
it is common to see abnormal mediastinal densities, related to the
different great vessel anatomy and orientation. A narrow mediastinum
is commonly seen in patients with associated d-transposition of
the aorta. In the presence of pulmonary atresia an acute angle may
be seen at the left heart border because of the absence of a normal
main pulmonary artery contour.
++
Chest X-ray can be particularly helpful in patients with heterotaxy (eFig. 498.8), in whom radiographic evidence of
abnormal visceral and bronchial situs, cardiac position, and lung segmentation
can be elucidated. An unbalanced complete atrioventricular canal
is suspected in patients with associated cardiac malpositions on
chest X-ray, such as isolated dextrocardia, levocardia with situs
inversus, or ambiguous, or mesocardia.
++
++
Excessive cardiomegaly suggests the onset of ventricular dysfunction,
often associated with severe regurgitation of the atrioventricular
valves, or systemic outflow obstruction.
++
Signs of pulmonary venous hypertension out of proportion compared
to the amount of pulmonary blood flow are seen when there is insufficiency
or stenosis of the left atrio-ventricular valve with a restrictive
atrial septum, or when there is anomalous pulmonary-venous connection
with obstruction.
++
Definitive diagnosis is usually made by echocardiography, which allows
sequential determination of (1) thoracoabdominal situs; (2) systemic
venous and pulmonary venous connections; (3) atrioventricular and
ventriculoarterial alignments and connections17-19 (eFig. 498.8); (4) morphology and function
of the single ventricle or dominant ventricle, and the atrioventricular valves
(eFigs. 498.9 and 498.10);
(5) conotruncal anatomy (position of the infundibular outlet chamber
and size of the bulboventricular foramen, if present);18,19 (6)
aortic arch and pulmonary arterial anatomy; and (7) the presence
of a ductus arteriosus or other aortopulmonary connection.15
++
Each anatomic variant has specific echocardiographic features
that characterize the lesion. Rarely, the anatomy cannot be elucidated
in detail and angiography or magnetic resonance is required. Echocardiography
is a routine essential test in the management of these patients
at all times throughout their lives. In the teenager and young adult,
transesophageal echocardiogram may be necessary to delineate the
anatomy well.
++
++
+++
Cardiac Magnetic
Resonance Imaging (MRI) and Computerized Tomography (CT)
++
Cardiac magnetic resonance imaging (MRI) and/or computed
tomography (CT) angiography can these days elucidate the anatomic features
of most complex heart defects accurately. CT has the disadvantage
of requiring significant ionizing radiation exposure. Gadolinium-enhanced
three-dimensional magnetic resonance angiography can demonstrate
the anatomy beautifully, especially for pulmonary arterial or arch
abnormalities (eFig. 498.11). In addition,
MRI is the best methodology to assess ventricular dynamics, especially
when the underlying anatomy is that of a single right ventricle.20,21 In
small children, heart-rate-gated studies to obtain high-quality
images of intracardiac anatomy and coronary arteries can be difficult to
succeed, given the baseline tachycardia.
++
+++
Catheterization
and Angiography
++
There are very few conditions for which diagnostic cardiac catheterization
and angiography continues to be performed prior to an initial surgical
intervention. Anatomic definition of cardiac and vascular structures
usually can be determined by echocardiography or if necessary, cardiac
magnetic resonance imaging (MRI)21 or computerized
tomography (CT) angiography. Patients with pulmonary atresia and
small central pulmonary arteries continue to undergo diagnostic
angiography in many centers, to delineate the anatomy of major aortopulmonary collateral
vessels prior to staged repair. These patients rarely have single
ventricle physiology, however. Patients with asplenia syndrome sometimes
have mixed pulmonary venous connection which may require diagnostic
cardiac catheterization to fully define. In addition, patients with
pulmonary atresia and intact ventricular septum usually undergo
diagnostic cardiac catheterization prior to surgical intervention
to determine the presence of right ventricle-dependent coronary
arterial circulation.
++
Following the early staged surgical procedures, cardiac catheterization
continues to be performed routinely in most patients prior to the
next stage, as well as in those patients who have postoperative complications
potentially requiring intervention.22 Anatomic
features of the single ventricle can be demonstrated nicely on angiography
(eFig. 498.12).23 However,
the main purpose of the study usually is to assess residual lesions
and intervene as necessary (eFig. 498.13 A,B).
For example, pulmonary artery stenosis is sometimes seen at the site
of a previous shunt or pulmonary artery banding. Venocameral or
pulmonary arteriovenous fistulas may develop after a bidirectional
Glenn procedure, residual left to right shunts, or aortopulmonary
collateral vessels may require embolization.22,24,25
++
++
++
Some consider that patients who are at low risk may be assessed with
noninvasive methods and defer diagnostic cardiac catheterization
unless a potential problem is found (ie, postoperative coarctation
of aorta seen on MRI.21 Others recommend performing routine
preoperative diagnostic cardiac catheterization for all patients
with single ventricle variants outside of the neonatal period.
++
Diagnostic evaluation will help identify risk factors for surgical palliation
(Table 498-2). Information important for
decision making from a hemodynamic standpoint includes systemic
and pulmonary blood flow, pulmonary arterial pressure and vascular
resistance, and ventricular end-diastolic pressure.15,22 Patients
with elevated pulmonary vascular resistance are not candidates for
a Fontan procedure.
++
++
The management algorithm typically followed for patients with single
ventricle variants is illustrated in eFigure 498.14.
Graphics illustrating the various surgical interventions that can
be performed on these patients are shown in eFigures 498.15, 498.16, 498.17, 498.18, 498.19, 498.20, 498.21, 498.22, 498.23, and 498.24.27,34
++
++
++
++
++
++
++
++
++
++
++
++
Prior to surgical intervention, newborns with ductal-dependent
lesions are placed on prostaglandin E1 until surgery is performed. Newborns
who do not have a ductal-dependent lesion but have pulmonary stenosis
may have a good balance between systemic and pulmonary blood flow
once the ductus arteriosus closes, and may be discharged without an
initial surgical intervention. In the absence of an adequate degree
of pulmonary stenosis, heart failure may develop, as discussed above.
These patients may be managed with diuretics and afterload reduction,
or pulmonary artery banding, particularly those patients without
any pulmonary outflow obstruction.35,36
++
In order to balance pulmonary and systemic blood flow in the
intensive care unit, the intensivist typically manipulates pulmonary
vascular resistance, increasing it to minimize pulmonary blood flow
and maintain systemic perfusion.12,37 This may
be achieved either by using a closed hood to increase inspired
and pulmonary vascular resistance, or by using a hypoxic or hypercarbic
mixture, or by hypoventilation utilizing mechanical ventilation,
sedation and paralysis. Supplemental oxygen and hyperventilation
should be avoided, as well as any other factor that could lower
the pulmonary vascular resistance. Additional medical management
in the intensive care unit prior to surgery depends upon the patient’s
condition. Common drugs used for inotropic support in the perioperative
period include milrinone, low-dose dopamine, and epinephrine.12
+++
Following Surgical
Intervention
++
Significant alteration in physiology may occur with the surgical
intervention, although the initial neonatal palliative procedures
typically retains the same physiologic model of complete mixing
and circulations in parallel. After stage II, the circulation is
in series for the upper half of the body, but will not be completely
in series until after stage III, the modified Fontan procedure.
If the stage I palliation includes an aortopulmonary shunt, the
patient is placed on low dose aspirin (3–5 mg/kg/day)
as antiplatelet agent.15,16 Because a volume load
persists after stage I palliation, the patient commonly receives
diuretics, occasionally an afterload reducing agent (such as captopril),
and occasionally digoxin to maximize ventricular function. Infants
at this stage are typically in need of high-calorie formula, with
very careful monitoring of weight gain.16 They
have a fragile hemodynamic condition and little reserve, and may
require hospitalization during minor systemic illnesses. Respiratory
syncytial virus (RSV) vaccination is warranted.
++
After stage II (bidirectional Glenn procedure) and stage III
(Fontan procedure) patients are typically continued on afterload
reduction and sometimes digoxin, but diuretics are often discontinued.
Following stage II patients typically improve in growth parameters,
and can be weaned from high-calorie feeds because of a more stable
and efficient circulation—the single ventricle is volume
downloaded because pulmonary blood flow is directly provided to
the lungs, passively. However, other medical problems can present.
For example, chronic hypertension of the upper-body venous circulation
may cause pleural effusions and upper-body edema.
++
There is significant variability in the medical management of
patients with single ventricle.38,39 For instance,
some cardiologists use afterload reducing agents in all single ventricle
patients, and others only when there is evidence of ventricular
dysfunction, or only in patients who have a systemic right ventricle.
Some surgeons recommend warfarin use following Fontan procedure
initially, whereas others do not. Similarly, differences in management
are seen at every stage both in the medical and surgical arenas.
However, in general, some form of anticoagulation is always used,
and there is general consensus on the overall management approach
with regards to goals of interventions and approximate timing of
surgery.
+++
Interventional Cardiac Catheterization
++
Patients with single ventricle variants may require transcatheter
interventions early at presentation and prior to the initial palliative procedure.
Such is true for of patients with a restrictive atrial-septal defect
and left atrial outlet atresia or stenosis.22 Transcatheter
creation of a new atrial septal defect with septostomy and balloon
septoplasty may be life saving.
++
Newborn patients with single ventricle and ductal-dependent lesions can
sometimes be considered candidates for ductal stenting. In particular,
patients with hypoplastic left heart syndrome have been managed
by some with what is called a hybrid procedure, where the ductus
is stented by the interventional cardiologist12,27 (eFig. 498.25), while the surgeon places bilateral
pulmonary artery bands to decrease the pulmonary blood flow and
protect the pulmonary vascular bed. This becomes the initial palliative
procedure or stage I, followed by a comprehensive stage II surgical
procedure, when the patient undergoes arch reconstruction, removal
of bands, pulmonary artery plasty, and bidirectional Glenn procedure.
++
++
Following each palliative surgical stage, interventional cardiac
catheterization plays a significant role in optimizing hemodynamics
and treating potential causes of hemodynamic disturbances (Table 498-1).22 Sometimes,
emergency cardiac catheterization in the immediate postoperative
period to create a new or augment a fenestration, to close residual
defects, or balloon dilate/stent stenotic vessels is required
in a severely compromised patient.22 At other times,
interventions are performed later in the postoperative period in
patients with chronic symptoms.
++
Interventions during cardiac catheterization are common in patients with
single ventricle and these include coil embolization of venous anomalies24 or
aortopulmonary collaterals,25 balloon dilation
and/or stenting of branch pulmonary artery stenosis, pulmonary
valvotomy or balloon dilation of coarctation of the aorta, closure
of a prior surgical shunt, transcatheter closure of residual anterograde
flow through the pulmonary valve, transcatheter closure of fenestration
or baffle leaks, and so on (Table 498-1).
++
The pioneer surgical contributions to the care of these patients
have historically opened new horizons to patients who lacked therapeutic options
previously. The Blalock-Taussig (BT) shunt was introduced in 1945
to augment pulmonary blood flow.31 This is now
performed frequently during infancy in a modified fashion using
a Gore-Tex tube, in patients with single ventricle who have pulmonary
stenosis or atresia as the initial surgical palliation. eFigure 498.20 illustrates various types
of surgical shunts used to provide pulmonary blood flow.
++
In 1958, William Glenn created a direct anastomosis between the
superior vena cava and the right pulmonary artery, and proved that
the pulmonary vasculature can accommodate the systemic venous return
passively, without interposition of a ventricular pump.40,41 This
was an extraordinary concept at the time, and the procedure continues
to be done today, in a modified fashion (a bidirectional Glenn procedure,
with blood flow from the superior vena cava to both pulmonary arteries),
but still with the same physiologic consequences. The bidirectional
Glenn shunt physiologically is a bypass of the ventricles, creating
a more efficient circulation by imposing less volume work on the
ventricles (eFig. 498.21).
++
The next major step towards proving that a pulmonary ventricle
is not essential for survival in humans was the performance of the Fontan
procedure in the early 1970s, demonstrating that in patients with
tricuspid atresia, a complete bypass of the ventricles can be achieved
successfully by anastomosing the right atrium to the pulmonary artery
(eFig. 498.22).42-44 Some
patients who underwent that original surgery in the 1970s are still
alive today.45
++
The next major step was an aggressive neonatal surgical approach,
the Norwood procedure for patients with hypoplastic left-heart variants
(eFig. 498.16).46 It became
clear that patients could not only survive long-term without a right
ventricle with normal oxygen levels following the modified Fontan
procedure, but they could do so without a left ventricle. It was
this advance of neonatal cardiac surgery, hand in hand with improvements
in postoperative care and the progress in interventional pediatric
cardiology in the 1980s that management pathways were developed
for neonates and infants with hypoplastic left ventricle, aimed
at preserving their candidacy for Fontan palliation or heart transplantation.12,32
++
There are patients with single ventricle variants who still may
not be candidates for single ventricle palliation, and for whom
the only option is transplantation. Such is true for some severe
forms of pulmonary atresia and intact ventricular septum with severe
coronary arteriopathy, as well as patients with single ventricle
variants and dysplastic atrioventricular valves with significant
regurgitation or those with more than moderate ventricular dysfunction.
Stenting of the ductus can be performed pretransplant to avoid the
need for chronic use of prostaglandins while waiting for an organ.
In addition there are a few centers in the country who electively
offer transplantation as a first line therapy for single ventricle
variants which require a Norwood procedure otherwise.38 Intermediate
and long-term survival of either approach is comparable, but there
are not enough organs available to allow transplantation to be the
major option for these patients, so that most consider transplant
should be reserved for patients at higher risk or who have failed
single ventricle palliation.
+++
Staged Surgical
Palliation
++
The goals in the management of patients with single ventricle
variants include protection of the pulmonary vasculature by avoiding
elevation in pulmonary arterial blood flow and pressure, and preservation
of ventricular function by minimizing volume and pressure overload.
+++
First-Stage
Palliation
++
The first stage palliative procedure is typically performed in
a newborn or soon thereafter. The reported early operative mortality
for an aortopulmonary shunt in neonates can be as high 17%32;
however, this value continues to decrease as the years go by. If
performed after the neonatal period, the mortality is significantly
lower. The early operative mortality in the newborn with single
ventricle ranges from 8% to 25%, and depends on
the specific lesion, the presence of hemodynamic compromise or organ
dysfunction prior to surgery, and associated cardiac malformations.33 It
is highest in patients who require complex surgery, such as aortic
arch reconstruction or resection of subaortic stenosis, and in those
with complex lesions such as patients with heterotaxy and associated
anomalous pulmonary venous connections. Over the years the surgical
mortality for stage I palliation in the form of Norwood procedure
has continued to improve, as low as 12% for some centers
and patient populations.42 However, there is a
significant interstage mortality of up to 15%, mostly represented
by sudden death.12
++
Stent implantation in the patent ductus is becoming more popular as
an alternative to a surgical shunt, although the intermediate and
long-term results of this procedure are unknown.12
++
Some single ventricle lesions either have subaortic obstruction
at birth or are at risk of developing it, particularly when the
ventricle is unloaded by the bidirectional Glenn shunt.47,48 These
patients may benefit from a Damus-Kaye-Stansel anastomosis as part
of their staged palliation (eFig. 498.23). Patients
with hypoplastic left heart syndrome undergo a modified Norwood
procedure, which includes ascending aortic enlargement via modification
of the Damus-Kaye-Stansel procedure, aortic arch augmentation, atrial
septectomy, and either a Blalock-Taussig shunt or a right ventricle-to-pulmonary
artery conduit (eFig. 498.16).3,46 The
latter is a recent modification and is commonly referred to as the Sano
modification34 (eFig. 498.25).
It is thought to minimize the risk of interstage death because aortic diastolic
pressure is higher, putatively decreasing the risk of coronary ischemia.
++
The circulation resulting from the initial palliation is only
left in place for a short period of time (3–6 months),
as ventricular dysfunction may become significant over time. This
relates to the inherent volume overload of a shunted single ventricle
physiology (the systemic ventricle is providing both the systemic
and the pulmonary blood flow). Due to this volume load the ventricle
over time acquires more spherical shape, which leads to an increase
in the end-systolic stress (afterload), and reductions in ventricular
function.
+++
Second Stage
Palliation: The Bidirectional Glenn Procedure
++
Around 4 to 6 months of age, a bidirectional cavopulmonary anastomosis,
or Glenn procedure, is performed.3,49 Risk factors
are similar to those for the Fontan procedure, although patients
with risk factors are more likely to tolerate a bidirectional Glenn
rather than a Fontan. Following this procedure, there is more effective
pulmonary blood flow, as only desaturated upper body blood passes
into the lungs. Pulmonary blood flow decreases substantially but
systemic O2 saturation is usually quite adequate, at about
80 to 85%. In addition, venous return to the heart is markedly
decreased, leading to a reduction in atrial-filling pressures (eFig. 498.21). There is an immediate change
in ventricular geometry following a bidirectional Glenn because
of the decrease in ventricular volume and increase in the ventricular
mass/volume ratio).This can lead to subaortic stenosis
in certain single ventricle variants.47,48 A bidirectional
Glenn circulation is essentially nonpulsatile. However, there are
specific instances when it is pulsatile, such as when there is additional
pulmonary blood flow from either a shunt or anterograde flow across
the pulmonary valve. In these patients, the systemic oxygen saturation tends
to be higher as there is increased amount of pulmonary blood flow. Currently
the surgical mortality following bidirectional Glenn procedure is
less than 5%.
+++
Third Stage
Palliative Surgery: Fontan Procedure
++
Complete separation of systemic venous return from the heart (total
cavopulmonary bypass) is commonly called a modified Fontan procedure.
Many modifications of the initial Fontan procedure have been proposed
and performed. Originally, the anastomosis was created between the
atrial appendage and the pulmonary artery, directly or by interposition of
a conduit43,44 (Fig. 498-3). Later,
the anastomosis was made at the roof of the right atrium medial
to the entry point of the superior vena cava.50 Subsequently,
the entry point of the superior vena cava was used at the site of
anastomosis to the pulmonary artery and a baffle was used to direct
blood within the right atrium to the superior vena cava and the
pulmonary arteries (lateral tunnel)3,51 (eFig.
498.25). Currently, the extracardiac conduit is the preferred
technique used in most centers3,52 (eFig.
498.19 and Fig. 498-3). Many surgeons
prefer to add a fenestration or small hole (4 mm) within the Fontan
pathway allowing right-to-left shunting to serve as a pop-off, lowering
postoperative venous pressures.30 Patients with
a fenestrated Fontan circulation typically have oxygen saturation
in the high 80s to low 90s range. If the Fontan is unfenestrated,
then the oxygen saturations are almost normal (the only source of
desaturation comes from coronary venous return). Generally the Fontan
procedure is performed in patients between ages 2 and 5 years, depending
on the preference of the center.49
++
++
The surgical mortality of the Fontan procedure has improved significantly
over the past 2 decades, to less than 5% currently.3,42,52-55 Unfortunately,
recent reports suggest that a total cavopulmonary bypass, or the
Fontan circulation, is not without long-term consequences.54,55 Estimated
freedom from Fontan failure at 5 and 10 years has been reported
in the order of 90% and 87%, respectively,42,53 with
a continued risk of death of about 1% to 3% per
year.
+++
Morbidity after
Single Ventricle Palliation
+++
Postoperative
Aortopulmonary Shunt
++
Infants following stage I palliation are in compensated heart
failure, have difficulty in gaining weight, and have a limited reserve
in case of any concurrent illness. This limited reserve is associated
with a relatively high incidence of sudden death during this interstage period,
as discussed above. If the second stage is not feasible, these patients
tend to develop cardiomyopathy over time, and the chronic cyanosis
and polycythemia lead to a significant long- term risk of cerebrovascular
accident. They are also at high risk for endocarditis and arrhythmias.12,16,42,56
++
The total right heart bypass, or Fontan circulation, may become dysfunctional
for various reasons:
++
1. Postoperative bidirectional Glenn procedure
Patients palliated with a bidirectional Glenn procedure have persistent
cyanosis, so that they too are at risk from the deleterious effect
of chronic polycythemia. In addition, they are at risk of developing
pulmonary arteriovenous malformations which cause intrapulmonary shunting
of deoxygenated blood directly into the pulmonary veins, leading
to further desaturation.56,57 This complication
is reversible once the Fontan is completed,58 presumably
due to flow of hepatic venous blood into the pulmonary circulation.
The elevated upper body venous pressures also leads to formation
of venovenous and venocameral collateral vessels, which also exacerbates
the cyanosis,24 Last, chronic cyanosis leads to
the development of aortopulmonary collateral flow, which increases the
volume work of the single ventricle.
Exercise stress testing in these patients demonstrates that even when
the systemic saturation is adequate at rest (> 85%), there is
marked desaturation during exercise.59 Patients
with partial right heart bypass, either pulsatile or not, have markedly
depressed exercise capacity (48% of the estimated functional
capacity), directly in relationship with the level of systemic saturation.
The chronotropic response is normal, similar to what occurs with
cyanotic congenital heart defects.
2. Postoperative Fontan
a. Increase in the transpulmonary gradient: The difference between pulmonary
arterial and pulmonary venous pressure is the transpulmonary pressure
gradient and it should not exceed about 8 mmHg. Over time, it tends
to increase in the Fontan patient due to deficient pulmonary arterial
growth, pulmonary artery branch stenosis,60 chronic
pulmonary micro or macro thromboembolism,61 or
a progressive increase in pulmonary vascular resistance. This typically
translates into increase in pulmonary arterial and systemic venous
pressures. In these patients, oral anticoagulants should be routinely
prescribed. The clinical manifestations of elevated systemic venous
pressures are described below.
b. Myocardial failure: An increase in the systemic ventricular
end diastolic pressure due to myocardial failure leads to an elevation
in pulmonary venous pressure and subsequently in pulmonary arterial
and systemic venous pressure. This can occur in hand with atrioventricular
valve insufficiency.
c. Pulmonary venous obstruction: Pulmonary venous stenosis or
extrinsic compression, or obstruction between the left and right
atrium (in patients with hypoplastic left heart syndrome)
can also lead to elevated pulmonary venous and, subsequently, pulmonary
arterial and systemic venous pressures.
d. Systemic venous pathway obstruction: If there is obstruction
within the Fontan baffle or conduit, systemic venous hypertension
will occur proximal to the obstruction.
++
Clinical manifestations of Fontan failure include peripheral
edema, chronic pleural effusions, protein-losing enteropathy,62 decreased
exercise tolerance, chronic atrial arrhythmias, and chronic cyanosis
++
Sometimes there are mechanical problems related to the specific type
of Fontan procedure performed, which can be solved or improved greatly
with Fontan redo. Such occurs in patients who develop a giant right
atrium after an atriopulmonary anastomosis, or conduit obstruction
in extracardiac conduits. They may benefit from either redo or conversion
to a different type of Fontan.63
+++
Peripheral Edema
and Chronic Effusions
++
As manifestations of venous hypertension, extravascular fluid may
respond to anticongestive management. Cardiac catheterization may
be indicated to evaluate hemodynamics with a particular focus on
a possible, intervention to
relieve right- or left-sided obstruction. Protein losing enteropathy
occurs in up to 11% of the patients.62 They
present with chronic diarrhea, hypoproteinemia, hypoalbuminemia,
chronic edema, pleural effusions, ascites, pericardial effusions,
and increase of the fecal alpha-1 antitrypsin. This problem is thought
to be related to venous hypertension, although hemodynamic correlation
is not always present. Medical management includes maximization
of anticongestive therapy, and use of anticoagulation, steroids,
all with limited success. The prognosis is poor, and thus, intervention
is required. Creation of a Fontan fenestration is an option, to
lower venous pressures. Heart transplantation may be indicated,
but it is of increased risk.
++
Cyanosis can develop in the Fontan patient due to development
of a right-to-left shunt within the baffle or decompressing venous
collaterals to pulmonary veins or cardiac chambers. Other possibilities
include ventilation-perfusion (VQ) mismatch due to either parenchymal
lung disease or to the effects of chronic pulmonary thromboembolism.
Right-to-left shunting can often be resolved in the catheterization
laboratory by coil or device closure (eFig. 498.26).
++
++
Following staged surgical palliation sinus node dysfunction is
reported to be as high as 37%.64 Arrhythmias
may occur in the early postoperative period, particularly in patients
with high risk factors and poor postoperative hemodynamics. Among
these, atrial arrhythmias, junctional ectopic tachycardia, and even
ventricular arrhythmias may develop. Junctional ectopic tachycardia
can occur in the immediate postoperative period after total right
heart bypass,particularly in patients of less than age
3 years, and is a sign of poor prognosis.
++
Supraventricular tachycardia in the form of atrial flutter is
a serious problem following the Fontan procedure.65 In
the long-term follow-up, it seems to be less frequent in patients
with total cavopulmonary connection (external conduit Fontan) than
in those with atriopulmonary connection, although the follow-up
periods are not comparable. Management includes antiarrhythmic drugs,
pacemakers, and radiofrequency ablation, as well as Fontan redo.66 Fontan
redo is offered to those patients with an old-style Fontan connection
and severely dilated atria.
++
Patients with a Fontan circulation have mildly diminished functional
capacity by ergometry to about 70% of the estimated functional
capacity in association with mild desaturation and subnormal chronotropic
response.59
+++
Pregnancy in
Single Ventricle Patients
++
Although limited reported experience demonstrated feasibility
of a successful pregnancy in single ventricle mothers, there is
significant morbidity and potential mortality related to it. Forty-five percent
of pregnancies resulted in live births in a study of 33 pregnancies.67