Chapter 498. The Patient with Single Ventricle

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. 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).

Electrocardiography

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

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.

Echocardiography

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

Medical Management

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).

Surgical Management

Historic Perspective

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.

Surgical Management

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. 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

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